2-(Trifluoromethyl)oxirane → [(S)-5-(3,3,3-Trifluoro-2-hydroxy-propyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid tert-butyl ester

HRID 31051

Reaction equation

[C:1]([O:5][C:6](=[O:24])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[C:10]2[CH:20]=[CH:21][CH:22]=[CH:23][C:9]1=2)([CH3:4])([CH3:3])[CH3:2].[F:25][C:26]([F:31])([F:30])[CH:27]1[O:29][CH2:28]1>CN(C=O)C.C(OCC)(=O)C.O>[C:1]([O:5][C:6](=[O:24])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:28][CH:27]([OH:29])[C:26]([F:31])([F:30])[F:25])[C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[C:10]2[CH:20]=[CH:21][CH:22]=[CH:23][C:9]1=2)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 90 °C

Procedure

((S)-6-Oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-carbamic acid tert-butyl ester (108 mg, 0.33 mmol) and 1,1,1-trifluoro-2,3-epoxypropane (762 mg, 6.7 mmol) were dissolved in DMF (2 ml) and heated to 90° C. for 4 h in a sealed tube. After addition of another 500 mg of 1,1,1-trifluoro-2,3-epoxypropane, heating was continued for 18 h. The mixture was diluted with ethyl acetate and water (10 ml each), separated and the aqueous phase extracted twice with each 10 ml ethyl acetate. The combine organic phases are dried over magnesium sulfate and evaporated to dryness. Chromatography (silica, eluent heptanes/ethyl acetate gradient from 1 to 30%) afforded the title compound as white solid (76%). MS: m/e=437(M+H+).

Workup

temperatureheating
customseparated
extractionthe aqueous phase extracted twice with each 10 ml ethyl acetate
dry with materialThe combine organic phases are dried over magnesium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-fd4c0dd8cdad42c99f8b14c94dda3323
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425551B2

Linked notes

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