Toluene → 2-Amino-6-(2-cyanoethyl)-nicotinic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH2:11])=[N:6][C:5]=1[NH2:12].[C-:14]#[N:15].C([Al+]CC)C.C1(C)C=CC=CC=1.[Cl-].[Na+]>O1CCCC1>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:14]#[N:15])=[N:6][C:5]=1[NH2:12]Participants
Procedure
To a solution of 2-amino-6-vinyl-nicotinic acid methyl ester (760 mg, 4.26 mmol) in tetrahydrofuran (76 mL) was added a solution of diethyl aluminum cyanide in toluene (12.8 mL, 12.8 mmol) dropwise under sodium chloride—an ice bath cooling, at an internal temperature of −5° C. or below, then, the solution was gradually allowed to room temperature and stirred overnight. The reaction solution was partitioned into an aqueous solution of saturated ammonium chloride and ethyl acetate. This organic layer was separated, washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography, and the title compound (180 mg, 0.878 mmol, 21%) was obtained as a yellow oil.
Workup
- temperaturecooling, at an internal temperature of −5° C. or below
- customwas gradually allowed to room temperature
- customThe reaction solution was partitioned into an aqueous solution of saturated ammonium chloride and ethyl acetate
- customThis organic layer was separated
- washwashed with brine
- dry with materialdried over anhydrous magnesium sulfate
- customThe solvent was evaporated in vacuo
- customthe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-1fad45fe537746ec9e4f9f66498ed0a5
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07932272B2
Reaction notes
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