Carbon Dioxide → 4-[(2S)-4-((1R)-1-phenylethyl)-morpholin-2-yl]-benzoic acid

HRID 1091385Notes

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.[C:27](=[O:29])=[O:28]>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]([C:27]([OH:29])=[O:28])=[CH:3][CH:4]=3)[CH2:9]2)[CH3:15])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a suspension of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (3.46 g, 10.0 mmol) in tetrahydrofuran (80 ml) was added n-butyllithium (7.7 ml, 12.0 mmol, 1.56 M in hexane) at −78° C. After stirring for 10 minutes, excess of dry ice was added to the mixture and the reaction mixture was maintained at −78° C. for 1.5 hours and then partitioned between diethyl ether and 0.2 N aqueous sodium hydroxide. The aqueous layer was washed with diethyl ether and neutralized with 1N hydrochloric acid. The resulting aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. Filtration of the precipitate gave 4-[(2S)-4-((1R)-1-phenyl-ethyl)-morpholin-2-yl]-benzoic acid (3.05 g, 98%) as white crystals.

Workup

additionwas added to the mixture
custompartitioned between diethyl ether and 0.2 N aqueous sodium hydroxide
washThe aqueous layer was washed with diethyl ether and neutralized with 1N hydrochloric acid
extractionThe resulting aqueous layer was extracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
filtrationFiltration of the precipitate

Sources & evidence

ORD record: ord-ff8e583abc69486d869f56df0b13e052
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129377B2

Reaction notes

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