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Reactions (10)
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Substances (3)
Citations (13)
Conditions
References
1
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Rx-ID: 1484526 Find similar reactions
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T=0°C;
Flitsch, Wilhelm; Kneip, Heinz-Gerd
Liebigs Annalen der Chemie, 1985 , # 9 p. 1895 - 1903 Title/Abstract Full Text Show Details
in water
BAYER PHARMACEUTICALS CORPORATION
Patent: WO2004/7502 A1, 2004 ; Location in patent: Page 15 ;
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Title/Abstract Full Text Show Details
1.2:
In a 50 mL flask was placed the product of step 1 [( (3),] X is CH2,2. 0 g, 13.5 mmol, [1] equiv) and cyanoacetamide (4) (1.24 g, 14.7 [MMOL,] 1.09 equiv) in 10 mL of water and 1 mL of piperidine acetate (prepared by adding 7.2 mL of piperidine to a cold solution of 4.2 mL acetic acid in 10.0 mL of water). This was [REFLUXED] for 3.5 h at which point 1.5 mL of acetic acid was slowly added to the hot solution. This caused vigorous boiling and effervescence. The mixture was allowed to stir to room temperature overnight. The precipitated solids were then filtered off and washed with water (30 mL) to provide only 422 mg (2.4 [MOL, 18percent)] of the desired product as a white [SOLID.APOS;H-NMR] (DMSO-d6) [612.] 26 (s, [1H),] 7.87 (s, 1H), 2.55 (t, 2H), 2.41 (t, 2H), 1.65 (m, 4H). in dimethyl sulfoxide
Product distribution / selectivity;
GIVAUDAN SA
Patent: WO2009/39675 A1, 2009 ;
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Location in patent: Page/Page column 8; 11-12 ; Title/Abstract Full Text Show Details
1; 2:
At room temp., a piperidinium acetate solution, freshly prepared by mixing piperidine (110 μL, 1.10 mmol) and acetic acid (65.0 μL, 1.10 mmol) in dimethyl sulfoxide (5.00 ml_), was injected into a stirred solution of the prepared oct-6-ynal (6.70 g, 54.0 mmol) and malonic acid (11.2 g, 108 mmol) in dimethyl sulfoxide (200 ml_). After refluxing the reaction mixture for 4 h, water (50 mL) and ether (100 mL) were added at room temp., and the layers were separated. The aqueous layer was extracted with ether (3 * 100 mL), and the combined organic extracts were washed with water (100 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude material (GC, δ3:δ2 = 70:30) was purified by chromatography on silica gel [200 g; pentane-Et2O (4:1); Rf = 0.24 in pentane-Et2O (5:1)] and subsequent Kugelrohr distillation at 160 °C/13 mbar to afford (3.pound.)-dec-3-en-8-ynoic acid (3.79 g, 42percent) as a colourless crystalline solid (mp, 40-43 0C).IR (neat): v 2937, 2860 (O-H), 1689 (C=O), 1347 (CH3), 964 (C=C, trans) cm"1. 1H NMR (CDCI3): δ 1.56 (quint, J = 7.0 Hz, 2 H, 6-H2), 1.78 (t, J = 2.5 Hz, 3 H, 10-H3), 1.99-
2.18 (m, 4 H, 5-, 7-H2), 3.08 (td, J = 1.0, 6.0 Hz, 2 H, 2-H2), 5.50-5.63 (m, 2 H, 3-, 4-H), 11.34 (br. s, 1 H1 OH).13C NMR (CDCI3): δ 3.4 (q, C-10), 18.1 (t, C-7), 28.3 (t, C-6), 31.5 (t, C-5), 37.8 (t, C-2), 75.7 (s, C-9), 78.8 (s, C-8), 121.5 (d, C-3), 134.4 (d, C-4), 178.8 (s, C-1). MS: m/z (percent) 41 (100) [C3H5+], 45 (24) [CO2H+], 53 (68) [C4H5+], 60 (7) [CH3CO2H+], 66 (39) [C5H6+], 70 (40) [C5H10+], 93 (68) [C7H9+], 106 (59) [M+- CH3CO2H], 112 (9) [C6H8O2+], 121 (28) [M+- CO2H], 133 (3) [M+- H2O - CH3], 138 (2) [M+- C2H4], 147 (1) [M+- H - H2O], 151 (5) [M+- CH3], 165 (2) [M+ - H], 166 (1) [M+].; At room temp., a piperidinium acetate solution, freshly prepared by mixing piperidine (35.0 μL, 0.354 mmol) and acetic acid (19.0 μL, 0.332 mmol)
in dimethyl sulfoxide (1.00 mL), was injected into a stirred solution of the prepared hept-5-ynal (1.50 g, 13.6 mmol) and malonic acid (2.83 g, 27.2 mmol) in dimethyl sulfoxide (50 mL). After refluxing the reaction mixture for 4 h, water (10 mL) and ether (20 mL) were added at room temp., and the layers were separated. The aqueous layer was extracted with ether (3 x 25 mL), and the combined organic extracts were washed with water (25 mL), dried (Na2SO4), and concentrated under reduced pressure. Kugelrohr distillation at <n="13"/>149 °C/14 mbar furnished (3.pound.)-non-3-en-7-ynoic acid (902 mg, 44percent) as colorless crystals (mp 43-45 0C).IR (neat): v 2916 (CMH)1 1691 (C=O), 1335 (CH3), 969 (C=C, trans) cm"1. 1H NMR (CDCI3): δ 1.77 (t, J = 2.5 Hz, 3 H, 9-H3), 2.18-2.24 (m, 4 H, 5-, 6-H2), 3.10 (dd, J = 1.0, 6.0 Hz, 2 H, 2-H2), 5.54-5.70 (m, 2 H, 3-, 4-H), 11.36 (br. s, 1 H, OH) ppm. 13C NMR (CDCI3): δ 3.4 (q, C-9), 18.8 (t, C-6), 32.0 (t, C-5), 37.7 (t, C-2), 76.1 (s, C-8), 78.3 (s, C-7), 122.0 (d, C-3), 133.6 (d, C-4), 178.5 (s, C-1) ppm. - MS: m/z (percent) 45 (20) [CO2H+], 53 (100) [C4H5+], 57 (89) [C4H9+], 60 (7)
[CH3CO2H+], 79 (33) [C6H7+], 92 (42) [M+ - CH3CO2H], 93 (97) [M+ - CH3CO2], 99 (3) [M+- C4H5], 107 (68) [M+- CO2H], 124 (2) [M+- CO], 137 (3) [M+- CH3], 151 (7) [M+- H], 152 (1) [M+].
in water
Merck and Co., Inc.
Patent: US6350745 B1, 2002 ; Location in patent: Page column 18 ; Title/Abstract Full Text Show Details
in water
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Corvas International, Inc.
Patent: US6342504 B1, 2002 ; Location in patent: Page column 50 ; Title/Abstract Full Text Show Details
11:Example 11 Preparation of 6-methylpyrid-2-one-3-carbonitrile
piperidine acetate (140 mmole, prepared by adding piperidine to a solution of 8.0 ML of acetic acid in 20 ML water until the solution was greater than PH 7) in water
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BAYER PHARMACEUTICALS CORPORATION
Patent: WO2005/87778 A1, 2005 ; Location in patent: Page/Page column 15-16 ; Title/Abstract Full Text Show Details
1.2:
Step 2: Synthesis of 2-hydroxy-5, 6, 7, 8-tetrahvdro-3-auinolinecarbonitrile : (5) X is CH2; In a 50 mL flask was placed the product of step 1 ( (3), X is CH2,2. 0 g, 13.5 mmol, 1 equiv) and cyanoacetamide (4) (1.24 g, 14.7 mmol, 1.09 equiv) in 10 mL of water and 1 mL of piperidine acetate (prepared by adding 7.2 mL of piperidine to a cold solution of 4.2 mL acetic acid in 10.0 mL of water). This was refluxed for 3.5 h at which point 1.5 mL of acetic acid was slowly added to the hot solution. This caused vigorous boiling and effervescence. The mixture was allowed to stir to room temperature overnight. The precipitated solids were then filtered off and washed with water (30 mL) to provide only 422 mg (2.4 mmol, 18percent) of the desired product as a white solid.'H-NMR (DMSO-d6) 8 12.26 (s, 1H), 7. 87 (s, 1H), 2.55 (t, 2H), 2.41 (t, 2H), 1.65 (m, 4H). in water
Hussein, Ahmed M.; Ahmed, Osama M.
Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 7 p. 2639 - 2644 Title/Abstract Full Text View citing articles Show Details
in diethyl ether; pentane
T=0 - 20°C;
Zumbansen, Kristina; Doehring, Arno; List, Benjamin
Advanced Synthesis and Catalysis, 2010 , vol. 352, # 7 p. 1135 - 1136 Title/Abstract Full Text View citing articles Show Details
in water
SCHERING CORPORATION
Patent: WO2006/98961 A2, 2006 ; Location in patent: Page/Page column 102 ;
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Title/Abstract Full Text Show Details
1.B: 2-Formyl-4-isopropylcyclohexanone (0.526 g, 3.13 mmol) was suspended in H2O (6.5 mL), and a solution of piperidine acetate [prepared from piperidine (0.94 mL, 3 equiv.), acetic acid (0.54 mL, 3 equiv.) and H2O (1.8 mL)] was added, followed by 2-cyanothioacetamide (0.323 g, 1.03 equiv.). The mixture was heated to 100 °C over 15 min., and then stirred for 40 min. at 100 °C. Acetic acid (2 mL) was added, and the reaction mixture was slowly cooled to room temperature. The reaction was filtered and the resulting solid was dried under vacuum. The crude 2-mercapto-6-isopropyl-5,6,7,8-tetrahydroquinoline-3- carbonitrile product (0.275 g) was used without further purification. in water
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ABBOTT LABORATORIES
Patent: WO2007/76034 A2, 2007 ; Location in patent: Page/Page column 75-76 ;
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8.8B:
Example 8B; 6-Isopropyl-2-oxol,2-dihydro-pyridine-3-carbonitrile; [0289] To a solution of the product of Example 8A (5.35 g, 0.0393 mol) and 2-cyanoacetamide (3.47 g, 0.0413 mol) in water (35 mL) was stirred at room temperature for 10 minutes. To this <n="77"/>mixture was added 2.5 mL of a stock piperidine acetate solution (prepared from 9.8 mL of piperidine, 6 mL of acetic acid and 10 mL of water), and the solution was heated under reflux for 2 hours. The mixture was then cooled to room temperature and taken to pH 4 by the addition of glacial acetic acid. The resulting light yellow solid was isolated by vacuum filtration, rinsed with water (2 x 30 mL), and dried under vacuum to provide the title product (4.36 g, 68percent).
2
A
B
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Rx-ID: 24154103 Find similar reactions
QIAGEN Genomics, Inc.
Patent: US6623928 B2, 2003 ; Title/Abstract Full Text Show Details
H:H.
H. Methylpyrrolidine acetate A stock solution of 1 molar piperidine acetate was prepared by mixing one equivalent of glacial acetic acid in an appropriate volume of water and slowly adding one equivalent 1-methylpyrrolidine. The pH of the stock solution is 7. The stock solution was diluted in an appropriate volume of water or acetonitrile to working concentration.
3
A
B
C
D
E
F
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B
C
D
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With acetic acid
Ambient temperatureeffect of AcOH ratio; MechanismProduct distribution;
Cristau; Darviche; Torreilles; Fabre
Tetrahedron Letters, 1998 , vol. 39, # 15 p. 2103 - 2106 Title/Abstract Full Text View citing articles Show Details
A
4
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5
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A
B
C
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With acetic acid
Ambient temperatureAcOH : Educt ratio = 10;
Cristau; Darviche; Torreilles; Fabre
Tetrahedron Letters, 1998 , vol. 39, # 15 p. 2103 - 2106 Title/Abstract Full Text View citing articles Show Details
With acetic acid
Ambient temperatureAcOH : Educt ratio = 10; Yield given;
Cristau; Darviche; Torreilles; Fabre
Tetrahedron Letters, 1998 , vol. 39, # 15 p. 2103 - 2106 Title/Abstract Full Text View citing articles Show Details
Rx-ID: 4966488 Find similar reactions
With water; acetic acid
Ambient temperature;
Cristau; Darviche; Torreilles; Fabre
Tetrahedron Letters, 1998 , vol. 39, # 15 p. 2103 - 2106 Title/Abstract Full Text View citing articles Show Details
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B: 80%
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6
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in water
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Patent: US3948903 A1, 1976 ;
Rx-ID: 25259415 Find similar reactions
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Title/Abstract Full Text Show Details
16:A.
This salt is dissolved in 150 ml. of water and the solution is treated with 42 g. of 2-cyanoacetamide and with a solution of piperidine acetate prepared from 4.2 ml. of glacial acetic acid, 11 ml. of water and enough piperidine to render the solution basic to litmus. The resulting mixture is heated at reflux for 3 hours, treated with activated charcoal and filtered. The filtrate is acidified with acetic acid and cooled. The nitrile product is collected by filtration and dried; m.p. 237°-239° C. (dec.) after trituration with ethanol.
7
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Rx-ID: 25259419 Find similar reactions
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in water; acetic acid; mineral oil; benzene
Parke, Davis and Company
Patent: US3948903 A1, 1976 ;
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Title/Abstract Full Text Show Details
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1:A.
1. 6-Cyclopentylmethyl-1,2-dihydro-2-oxonicotinonitrile; a mixture of 26.5 g. of cyclopentyl-2-propanone and 21 g. of ethyl formate is added dropwise with cooling to a stirred mixture of 18.2 g. of a 57percent sodium hydride dispersion in mineral oil and 250 ml. of benzene. The resulting thick suspension is stirred at room temperature for 20 hours and is then treated with 100 ml. of water. The aqueous phase is separated and the organic phase extracted with water. The combined aqueous phase and aqueous extract is washed with ether. To the resulting aqueous solution, containing the sodium salt of 4-cyclopentylacetoacetaldehyde, is added 17 g. of 2-cyanoacetamide, 6 g. of glacial acetic acid and a solution of piperidine acetate prepared from 5 g. of glacial acetic acid, 10 ml. of water and enough piperidine to give a basic reaction to litmus. The resulting solution is heated at reflux for 4 hours, cooled and acidified with acetic acid. The product which separates, 6-cyclopentylmethyl-1,2-dihydro-2-oxonicotinonitrile, is collected by filtration and washed with ether; m.p. 135°-140° C. after crystallization from ethyl acetate. In a similar manner, the following nitriles are prepared.
8
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Rx-ID: 25259420 Find similar reactions
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in water; acetic acid; mineral oil; benzene
Parke, Davis and Company
Patent: US3948903 A1, 1976 ;
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11:A.
11. 6-(p-Chlorobenzyl)-1,2-dihydro-2-oxonicotinonitrile; from a solution of the sodium salt of 4-(p-chlorophenyl)acetoacetaldehyde (in 100 ml. of water, prepared from 9.1 g. of a 57percent sodium hydride dispersion in mineral oil 200 ml. of benzene, 19.9 g. of p-chlorophenyl-2-propanone and 13.2 g. of ethyl formate), 9.0 g. of 2-cyanoacetamide, 4 ml. of glacial acetic acid and a solution of piperidine acetate prepared from 2.5 ml. of glacial acetic acid, 5 ml. of water and enough piperidine to render the solution basic to litmus; m.p. 205°-210° C. after crystallization from acetonitrile.
9
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Rx-ID: 25259421 Find similar reactions
in water; mineral oil; benzene
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Parke, Davis and Company
Patent: US3948903 A1, 1976 ; Title/Abstract Full Text Show Details
13:A.
13. cis-2,4b,5,6,7,8,8a,9-Octahydro-2-oxo-1H-indeno[2,1-b]pyridine-3-carbonitrile; from a solution of the sodium salt of hexahydro-2-oxo-1-indancarboxaldehyde (in 100 ml. of water, prepared from 10.1 g. of a sodium hydride dispersion in mineral oil, 200 ml. of benzene, 16.1 g. of hexahydro-2-indanone and 17.2 g. of ethyl formate), 10 g. of 2-cyanoacetamide, and a solution of piperidine acetate prepared from 3.5 ml. of glacial acetic acid, 10 ml. of water and enough piperidine to render the solution basic to litmus; m.p. 244°-246° C. after crystallization from methanol.
10
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Rx-ID: 25259422 Find similar reactions
in water; mineral oil; benzene
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Parke, Davis and Company
Patent: US3948903 A1, 1976 ; Title/Abstract Full Text Show Details
14:A.
14. 6-Furfuryl-1,2-dihydro-2-oxonicotinonitrile; from a solution of the sodium salt of 4-(2-furyl)acetoacetaldehyde (in 100 ml. of water, prepared from 13.7 g. of a 57percent sodium hydride dispersion in mineral oil, 350 ml. of benzene, 13.7 g. of (2-furyl)-2-propanone and 20.3 g. of ethyl formate), 13.6 g. of 2-cyanoacetamide, and a solution of piperidine acetate prepared from 2 g. of glacial acetic acid, 10 ml. of water and enough piperidine to render the solution basic to litmus.