Trifluoroacetic acid → N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one

HRID 1977800Notes

Reaction equation

[CH2:1]([N:8]1[CH:13]=[CH:12][O:11][C:10](=[O:14])[CH:9]1[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(OC(C)C)(=O)C>C(#N)C>[CH2:1]([N:8]1[CH:13]=[CH:12][O:11][C:10](=[O:14])[C@@H:9]1[C:15]1[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A futher batch of N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one (−)-3BCS salt was prepared substantially according to the previous method except that the following quantities and reaction conditions were used: N-benzyl-3-(4-fluorophenyl)-1,4-oxazin-2-one (racemate) (4.96 g); (−)-3BCS in acetonitrile (1.85M; 9.4 ml); trifluoroacetic acid (2.1 ml); and isopropyl acetate (55 ml). The mixture was stirred at 90° C. for 6 days and then cooled to 0-5° C. and aged for 1 hour. The solid N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one (−)-3BCS salt was collected and washed with isopropyl acetate (20 ml). Yield 9.40 g (90%); ee 99.6% (S) isomer. The chiral composition of the remaining liquors was determined as 88% (R), 12% (S).

Workup

customaccording to the previous method except that the following quantities and reaction conditions
temperaturecooled to 0-5° C. and aged for 1 hour
customThe solid N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one (−)-3BCS salt was collected
washwashed with isopropyl acetate (20 ml)

Sources & evidence

ORD record: ord-1b16a95fe1144e838fbb7f8caab05e90
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06235735B1

Reaction notes

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