Ammonia → HCID 68630905, compound
Reaction equation
C([O:4][C:5]([C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([CH2:14][CH:15]([CH3:17])[CH3:16])=[CH:9][N:8]=1)=O)(C)C.[NH3:18]>CO>[CH2:14]([C:10]1[C:11]([CH3:13])=[CH:12][C:7]([C:5]([NH2:18])=[O:4])=[N:8][CH:9]=1)[CH:15]([CH3:17])[CH3:16]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
A solution of 5-isobutyl-4-methyl-pyridine-2-carboxylic acid isopropyl ester (655 mg, 2.78 mmol, prepared in analogy to the corresponding ethyl ester) in 7 N NH3 in methanol (40 mL) is stirred in a sealed vial at 75° C. for 72 h. The solvent is removed in vacuo and the residue is dissolved again in 7 N NH3 in methanol. The resulting solution is again stirred at 75° C. for 24 h. The solvent is evaporated to give crude 5-isobutyl-4-methyl-pyridine-2-carboxylic amide (535 mg); LC-MS: tR=0.80 min; [M+1]+=193.01. This material is dissolved in DCM (20 mL) and pyridine (1.08 g, 11.13 mmol) is added. The mixture is stirred at rt for 5 min before trifluoroacetic acid anhydride (1.75 g, 1.18 mmol) is added dropwise. The mixture is stirred at rt for 16 h. The mixture is diluted with DCM (100 mL), washed with sat. aq. NaHCO3 solution (3×50 mL) and brine (50 mL). The org. extract is dried over Na2SO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give 5-isobutyl-4-methyl-pyridine-2-carbonitrile (106 mg) as a pale yellow oil; LC-MS: tR=0.96 min; [M+1]+=175.03.
Workup
- customThe solvent is removed in vacuo
- dissolutionthe residue is dissolved again in 7 N NH3 in methanol
- stirringThe resulting solution is again stirred at 75° C. for 24 h
- customThe solvent is evaporated
Sources & evidence
- ORD record
- ord-eabe3bd4c0c446f19b2f0954d0cd7e0e
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08575200B2
Reaction notes
Loading…