Dimethylformamide → 4-[(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl]benzaldehyde

HRID 218318Notes

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]=1

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (intermediate 13, 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-3bbe94ba33af4d1f842df36677700530
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198437B2

Reaction notes

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