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

HRID 1638157

반응식

HRID 1638157 반응식
[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]

참가 물질

6

반응물 4

HCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 111506973-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone

생성물 1

HCID 11089040beta-(R)-(2-fluorophenyl)-gamma,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-30 °C

실험 절차

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)2NNa, 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.

후처리

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

출처 및 근거

ORD 기록
ord-724b76e8e1424ee0b27432583bbfea09
출처 데이터셋
uspto-grants-2000_03
특허 번호
US06043365

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