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

Reaktionsgleichung

Reaktionsgleichung von HRID 1185864
[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]

Komponenten

5

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-c1d92ca87729459bb68440e33a15e628
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669234B2

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