2,2-Difluoro-2-(fluorosulfonyl)acetic acid → 4-Difluoromethoxy-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester

HRID 1185864

반응식

HRID 1185864 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[C:14]([O:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=1)=[O:19])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]([F:36])(S(F)(=O)=O)C(O)=O>CC#N.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][CH:28]([F:36])[F:27])[CH2:10][CH:9]1[C:14]([O:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=1)=[O:19])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 666209004-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester

생성물 1

HCID 666212034-Difluoromethoxy-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester수율 61%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
45 °C

실험 절차

To 4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester (500 mg) and Cu(I)I (45 mg) in MeCN (8 mL) at 45° C. was added 242 μl of difluoro-fluorosulfonyl-acetic acid in 2 mL of MeCN dropwise for 60 min. The reaction mixture was stirred at 45° C. for 60 min. and evaporated under reduced pressure, and resulting residue was taken up in ethyl acetate (100 mL). The organic phase was washed with brine (1×100 mL) and dried over sodium sulfate. After the solvent was removed, the resulting oil was subjected to silica gel chromatography using effluent of 10-50% ethyl acetate and hexanes. The fractions containing product were combined and the solvent was removed under reduced pressure to provide 4-Difluoromethoxy-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester (339 mg, 61%) as a clear oil.

후처리

  1. customevaporated under reduced pressure
  2. customresulting residue
  3. washThe organic phase was washed with brine (1×100 mL)
  4. dry with materialdried over sodium sulfate
  5. customAfter the solvent was removed
  6. additionThe fractions containing product
  7. customthe solvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-c1d92ca87729459bb68440e33a15e628
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669234B2

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