Methyl iodide → (4S)-3-{(2S)-1-oxo-2-[3,5-bis(trifluoromethyl)phenyl]propyl}4-(phenylmethyl)-2-oxazolidinone

HRID 2213004Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:11][C:12]([F:40])([F:39])[C:13]1[CH:14]=[C:15]([CH2:23][C:24]([N:26]2[C@@H:30]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:29][O:28][C:27]2=[O:38])=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.I[CH3:42].[Cl-].[NH4+]>O1CCCC1>[O:25]=[C:24]([N:26]1[C@@H:30]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:29][O:28][C:27]1=[O:38])[C@H:23]([C:15]1[CH:16]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:18]=[C:13]([C:12]([F:11])([F:39])[F:40])[CH:14]=1)[CH3:42]

Participants

Conditions

Temperature: -78 °C

Procedure

Sodium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 19.3 mL) was added slowly to a stirred, cooled (−78° C.) solution of (4S)-3-[3,5-bis(trifluoromethyl)benzeneacetyl]-4-(phenylmethyl)-2-oxazolidinone (Description 36, 7.25 g, 16.8 mmol) in tetrahydrofuran (60 mL) and the mixture was stirred at −78° C. for 1 hour. Iodomethane (21 mL, 33.6 mmol) was added and the mixture was stirred at −78° C. for 30 minutes, at 0° C. for 1 hour, then at room temperature overnight. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane:EtOAc (90:10 increasing to 85:15), to give the title compound as a colorless oil (5.14 g, 69%). 1H NMR (360 MHz, CDCl3) δ 7.84 (2H, s), 7.78 (1H, s), 7.38–7.27 (3H, m), 7.23–7.21 (2H, m), 5.26 (1H, q, J 7.0 Hz), 4.68–4.64 (1H, m), 4.19–4.15 (2H, m), 3.34 (1H, dd, J 3.3, 13.3 Hz), 2.83 (1H, dd, J 9.5, 13.3 Hz), and 1.60 (3H, d, J 7.0 Hz).

Workup

stirringthe mixture was stirred at −78° C. for 30 minutes, at 0° C. for 1 hour
customat room temperature
customovernight
extractionthe mixture was extracted with ethyl acetate
dry with materialThe combined organic fractions were dried (MgSO4)
customthe solvent was evaporated under reduced pressure
customThe residue was purified by flash column chromatography on silica gel
washeluting with isohexane:EtOAc (90:10 increasing to 85:15)

Sources & evidence

ORD record: ord-1f31d30f1bb44380b99baf81beb5f3d7
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07105507B2

Reaction notes

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