Dimethylformamide → 4-[(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl]benzaldehyde
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:29]=[O:30]>O1CCCC1>[C:16]1([C@H:14]([N:10]2[CH2:11][CH2:12][O:13][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([CH:29]=[O:30])=[CH:3][CH:4]=3)[CH2:9]2)[CH3:15])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1Participants
Conditions
- Temperature
- -10 °C
Procedure
To a solution of (2S)-2 (4-bromophenyl)-4 ((1R)-1-phenylethyl)morpholine (intermediate 1a, 63.3 g, 183 mmol) in tetrahydrofuran (450 ml) was added n-butyllithium (1.57 M in hexane solution, 175 ml, 275 mmol) at −78° C. and the mixture was stirred for 20 minutes. N,N-dimethylformamide (28.3 ml 365 mmol) was added and the mixture was stirred for 2 hours at −78° C. and then allowed to be warmed to −10° C. The reaction was quenched with aqueous ammonium chloride, and the resulting solution was partitioned between water and ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford crude 4-((2S)-4 ((1R)-1-phenylethyl) morpholin-2-yl)benzaldehyde (intermediate 14, 55.1 g). This compound was used without further purification.
Workup
- stirringthe mixture was stirred for 2 hours at −78° C.
- customThe reaction was quenched with aqueous ammonium chloride
- customthe resulting solution was partitioned between water and ethyl acetate
- washThe organic layer was washed with water and brine
- dry with materialdried over sodium sulfate
- customThe solvent was evaporated under reduced pressure
Sources & evidence
- ORD record
- ord-91ab3b04b58a49e394fddca88c53f890
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08518939B2
Reaction notes
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