2,2,2-Trifluoroethanol → (2S,4R)-1-tert-Butyl 2-methyl 4-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenylsulfonyl)pyrrolidine-1,2-dicarboxylate

HRID 1025332Notes

Reaction equation

HRID 1025332 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C@H:11]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:13]([C:23]([O:25][CH3:26])=[O:24])[CH2:12]2)(=[O:10])=[O:9])=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.[F:31][C:32]([F:36])([F:35])[CH2:33][OH:34].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[F:31][C:32]([F:36])([F:35])[CH2:33][O:34][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C@H:11]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[C@H:13]([C:23]([O:25][CH3:26])=[O:24])[CH2:12]2)(=[O:9])=[O:10])=[C:4]([C:27]([F:28])([F:30])[F:29])[CH:3]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 10796Cesium carbonateHCID 66771094(2S,4R)-1-tert-butyl 2-methyl 4-(4-fluoro-2-(trifluoromethyl)phenylsulfonyl)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 86646837(2S,4R)-1-tert-Butyl 2-methyl 4-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenylsulfonyl)pyrrolidine-1,2-dicarboxylateYield 65.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Under an atmosphere of argon, (2S,4R)-1-tert-butyl 2-methyl 4-(4-fluoro-2-(trifluoromethyl)phenylsulfonyl)pyrrolidine-1,2-dicarboxylate ([prepared in analogy to General Procedure C, steps C1-C3, using 2-trifluoromethyl-4-fluorothiophenol in step C2] 0.79 g, 1.73 mmol, Eq: 1.00) was combined with N,N-dimethylacetamide (10 ml) to give a light yellow solution. 2,2,2-Trifluoroethanol (416 mg, 301 μl, 4.16 mmol, Eq: 2.4) and cesium carbonate (1.02 g, 3.12 mmol, Eq: 1.8) were added. The reaction mixture was stirred over night at RT. The crude reaction mixture was concentrated in vacuo. The residue was poured into HCl (0.5 M, 20 ml) and extracted with ethyl acetate. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 40% ethyl acetate in heptane) to yield the title compound as a white foam (610 mg, 65.7%, MS (m/e)=536.1 [M+H+]).

Workup

  1. customto give a light yellow solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. additionThe residue was poured into HCl (0.5 M, 20 ml)
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 50 g, 0% to 40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-5b9bde2663f748b9a8a46a78b2cd15cf
Source dataset
uspto-grants-2014_05
Patent number
US08729061B2

Reaction notes

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