2,2,2-Trifluoroethanol → HCID 59543608, compound

HRID 1697664Notes

Reaction equation

HRID 1697664 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].C(=O)([O-])[O-].[Cs+].[Cs+].[C:13]([C:15]1([NH:18][C:19]([C@@H:21]2[CH2:25][C@@H:24]([S:26]([C:29]3[CH:34]=[CH:33][C:32](F)=[CH:31][C:30]=3[C:36]([F:39])([F:38])[F:37])(=[O:28])=[O:27])[CH2:23][N:22]2[C:40]2[N:41]([CH:46]3[CH2:49][CH2:48][CH2:47]3)[N:42]=[C:43]([CH3:45])[CH:44]=2)=[O:20])[CH2:17][CH2:16]1)#[N:14]>CN(C=O)C>[C:13]([C:15]1([NH:18][C:19]([C@H:21]2[CH2:25][C@@H:24]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[CH:31][C:30]=3[C:36]([F:37])([F:39])[F:38])(=[O:27])=[O:28])[CH2:23][N:22]2[C:40]2[N:41]([CH:46]3[CH2:49][CH2:48][CH2:47]3)[N:42]=[C:43]([CH3:45])[CH:44]=2)=[O:20])[CH2:17][CH2:16]1)#[N:14]

Participants

5

Reactant 3

HCID 64092,2,2-Trifluoroethanol2×HCID 10796Cesium carbonateHCID 66770568HCID 66770568, compound

Product 1

HCID 59543608HCID 59543608, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,2,2,-Trifluoroethanol (10 ul, 137 umol; CAS Reg. No. 75-89-8 99) and cesium carbonate (45 mg, 137 umol) were added to a solution of (2S,4R)-1-(2-cyclobutyl-5-methyl-2H-pyrazol-3-yl)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide (37 mg, 69 umol; example 388 g) in DMF (500 ul) under an argon atmosphere. The reaction mixture was stirred for 72 h at ambient temperature and partitioned between ice water/brine 1/1 and iPrOAc. The layers were separated and the aqueous layer was extracted one more time with iPrOAc. The combined extracts were washed with ice water/brine 1/1, dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give a yellow foam which was purified by preparative chiral HPLC to give the title compound (6 mg, 10 umol; 14%) as colorless oil. MS (ESI): m/z=620.2 [M+H]+.

Workup

  1. custompartitioned between ice water/brine 1/1 and iPrOAc
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted one more time with iPrOAc
  4. washThe combined extracts were washed with ice water/brine 1/1
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customto give a yellow foam which
  9. customwas purified by preparative chiral HPLC

Sources & evidence

ORD record
ord-f1d559b9f2684fc8a19d6e28f8c4d02b
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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