Sodium hydride → (S)-4-((R)-1,1-difluoropropan-2-yl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one

HRID 57380

반응식

HRID 57380 반응식
[F:1][CH:2]([F:11])[C@@H:3]([C@H:5]1[CH2:9][O:8][C:7](=[O:10])[NH:6]1)[CH3:4].[F:12][C:13]1[N:18]=[C:17](F)[CH:16]=[CH:15][N:14]=1.[H-].[Na+]>CN(C=O)C.C(OC(=O)C)C.[Cl-].[Na+].O.O>[F:11][CH:2]([F:1])[C@@H:3]([C@H:5]1[CH2:9][O:8][C:7](=[O:10])[N:6]1[C:15]1[CH:16]=[CH:17][N:18]=[C:13]([F:12])[N:14]=1)[CH3:4]

참가 물질

7

반응물 3

HCID 24758Sodium hydride3회HCID 1377162,4-DifluoropyrimidineHCID 90416634(S)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one

생성물 1

HCID 90415701(S)-4-((R)-1,1-difluoropropan-2-yl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one수율 58.7%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회HCID 23713072Sodium chloride dihydrate용매2회

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온도
5 °C

실험 절차

To a solution of (S)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (223 mg, 1.35 mmol) and 2,4-difluoropyrimidine (157 mg, 1.35 mmol) in DMF (4.09 mL) was added sodium hydride (60% wt.; 70.2 mg) in three portions at <0° C. (sodium chloride/ice). After the first portion of sodium hydride the mixture was stirred for ˜5 min. The remaining two portions of sodium hydride were added over ˜5 min and stirring was continued for 30 min. The mixture was diluted with ethylacetate (10 mL), stirred for 5 min and further slowly diluted with brine/water (1/1; 10 mL). The mixture was allowed to warm to 5° C. and poured into a mixture of brine/water (1/1; 20 mL) and ethylacetate (20 mL). The aqueous layer was separated and extracted with ethylacetate (25 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane] to provide (S)-4-((R)-1,1-difluoropropan-2-yl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (207 mg) as a white solid.

후처리

  1. stirringstirred for 5 min
  2. customThe aqueous layer was separated
  3. extractionextracted with ethylacetate (25 mL)
  4. washThe combined organic layers were washed with brine (40 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered off
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane]

출처 및 근거

ORD 기록
ord-8c6d70b3559e43b4a59cd382e889ebe3
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

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