Sodium hydride → (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one

HRID 57359노트

반응식

HRID 57359 반응식
[H-].[Na+].[Si:3]([O:20][CH2:21][C@H:22]1[CH2:26][O:25][C:24](=[O:27])[NH:23]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:28][C:29]1[N:34]=[C:33](F)[CH:32]=[CH:31][N:30]=1>CN(C=O)C>[Si:3]([O:20][CH2:21][C@H:22]1[CH2:26][O:25][C:24](=[O:27])[N:23]1[C:31]1[CH:32]=[CH:33][N:34]=[C:29]([F:28])[N:30]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 1377162,4-DifluoropyrimidineHCID 89766177HCID 89766177, 화합물

생성물 1

HCID 90416256(R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one수율 73%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Sodium hydride (34 mg, 0.84 mmol, 1.5 equiv) was carefully added to a solution of (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)oxazolidin-2-one (200 mg, 0.563 mmol) in DMF (2.8 mL). The mixture was stirred at room temperature for 20 minutes and then 2,4-difluoropyrimidine (0.072 mL, 0.84 mmol, 1.5 equiv) was added (bubbling). The yellow suspension was stirred for minutes and the reaction was then carefully quenched with saturated aqueous ammonium chloride (5 mL). Water (20 mL) was added and the mixture was extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (20 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 30%) provided (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (0.185 g, sticky colorless oil) in 73% yield. 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=5.8, 2.2 Hz, 1H), 8.12 (dd, J=5.8, 3.4 Hz, 1H), 7.58 (m, 2H), 7.48-7.32 (m, 6H), 7.23 (m, 2H), 4.80 (m, 1H), 4.65 (dd, J=8.6, 3.0 Hz, 1H), 4.55 (m, 1H), 4.18 (dd, J=11.1, 3.5 Hz, 1H), 3.83 (dd, J=11.1, 2.1 Hz, 1H), 1.04 (s, 9H). MS m/z 452.3 (M+H)+; Rt-1.15 min.

후처리

  1. custom(bubbling)
  2. stirringThe yellow suspension was stirred for minutes
  3. customthe reaction was then carefully quenched with saturated aqueous ammonium chloride (5 mL)
  4. additionWater (20 mL) was added
  5. extractionthe mixture was extracted with ethyl acetate (2×25 mL)
  6. washThe combined organic extracts were washed with saturated aqueous sodium chloride (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-cf2809937dce4b0f8a4165f036dc6fe0
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

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