Bromoacetonitrile → beta-(R)-(2-fluorophenyl)-gamma,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile

HRID 566262

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([N:11]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][O:13][C:12]1=[O:22])=[O:10].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].Br[CH2:34][C:35]#[N:36].[NH4+].[Cl-]>C1COCC1>[C:35]([CH2:34][C@H:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[C:9]([N:11]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][O:13][C:12]1=[O:22])=[O:10])#[N:36]

Participants

Conditions

Temperature: -30 °C

Procedure

To a solution of 3-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone (435 g, 1.45 mol) in THF (6000 mL), is added sodium hexamethyldisilazide [(TMS)2 NNa, 1M in THF, 1480 ml, 1.48 mol] dropwise at −78° C. The resulting mixture is then warmed to −30° C. and stirred for 2.5 hours. After this time the reaction mixture is recooled to −78° C. and a solution of BrCH2CN (175 g, 1.46 mmol) in THF (200 mL) is added. The reaction mixture is then warmed to −40° C. and stirred for 2 hours. Subsequently the resulting solution is treated with saturated NH4Cl (1×3000 ml) and extracted with EtOAc (1×3000 mL). The organic layer is separated, washed with H2O (1×1500 mL), saturated NaCl solution (2×1500 mL), dried over MgSO4 and concentrated in vacuo, to provide 3-[(R)-β-cyano-α-(2-fluorophenyl)-propionyl]-4-(R)-phenyl-2-oxazolidinone, m.p. 179-181° C.

Workup

customis recooled to −78° C.
temperatureThe reaction mixture is then warmed to −40° C.
stirringstirred for 2 hours
extractionextracted with EtOAc (1×3000 mL)
customThe organic layer is separated
washwashed with H2O (1×1500 mL), saturated NaCl solution (2×1500 mL)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c2e93f265b024263bee5e9b284bba3b8
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06174888B1

Linked notes

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