Chloroacetyl chloride → (6S)-4-benzyl-6-(4-fluorophenyl)morpholin-3-one

HRID 1671477Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([OH:18])[CH2:9][NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.Cl[CH2:20][C:21](Cl)=[O:22].C(N(CC)CC)C.NC(O)C.C[O-].[Na+]>C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[CH2:9][N:10]([CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:21](=[O:22])[CH2:20][O:18]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 2 °C

Procedure

To a suspension of (1S)-1-(4-fluorophenyl)-2-(benzylamino)ethanol (22.0 g, 89.69 mmol) in toluene (100 mL) was added dropwise over 1 hr a solution of chloroacetyl chloride (9.3 mL, 116.6 mmol) in toluene (30 mL) at 5-15° C. After stirring for 2 hrs, a solution of triethylamine (17.4 mL, 123.7 mmol) in toluene (20 mL) was added dropwise over 15 min to the mixture at 10-15° C. The mixture was stirred for 17 hrs at room temperature. After HPLC analysis to confirm a disappearance of the aminoethanol, the mixture was cooled to 2° C., and sodium methoxide (52 g, 269.07 mmol, 28% methanol solution) was added dropwise over 15 min. The mixture was stirred at 2-5° C. for 9 hrs, and water (60 mL) was added. The organic layer was separated and washed successively with 0.5N hydrochloric acid and saturated aqueous sodium hydrogencarbonate solution. The solvent was evaporated under reduced pressure to give (6S)-6-(4-fluorophenyl)-4-(benzyl)morpholin-3-one (27.78 g) as a yellow oil.

Workup

stirringThe mixture was stirred for 17 hrs at room temperature
stirringThe mixture was stirred at 2-5° C. for 9 hrs
customThe organic layer was separated
washwashed successively with 0.5N hydrochloric acid and saturated aqueous sodium hydrogencarbonate solution
customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record: ord-5ca75732571d471fb40fb64493e25b9d
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994315B2

Reaction notes

Loading…