Reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[CH:13]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:24])[CH3:23])=[CH:17][CH:16]=1)=[O:14]>CCCCCC.C1COCC1>[OH:14][CH:13]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)[C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:22](=[O:24])[CH3:23])=[CH:19][CH:20]=1Participants
Conditions
- Temperature
- -78 °C
Procedure
Butyllithium, 1.6M in hexane (146 ml) was added dropwise at −78° C. under N2 flow to a solution of 2-bromopyridine (0.1348 mol) in THF (300 ml). The mixture was stirred at −78° C. for 20 minutes. A solution of N-(4-formylphenyl)acetamide (0.1226 mol) in THF (300 ml) was added at −60° C./−70° C. The mixture was stirred at −60° C./−70° C. for 1 hour, then poured out into ice water and extracted with EtOAc. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue (27 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from diethyl ether and 2-propanone. The precipitate was filtered off and dried, yielding 5.09 g (17%) (±)—N-[4-[hydroxy(2-pyridinyl)methyl]phenyl]acetamide (compound 688).
Workup
- stirringThe mixture was stirred at −60° C./−70° C. for 1 hour
- extractionextracted with EtOAc
- customThe organic layer was separated
- customdried
- filtrationfiltered
- customthe solvent was evaporated
- customThe residue (27 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1)
- customThe pure fractions were collected
- customthe solvent was evaporated
- customThe residue was crystallized from diethyl ether and 2-propanone
- filtrationThe precipitate was filtered off
- customdried
Sources & evidence
- ORD record
- ord-ad60c003d8774bbc90565f966546623f
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07579352B2
Linked notes
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