Cesium fluoride → (2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 501641Notes

Reaction equation

HRID 501641 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[C:25]([F:28])([F:27])[F:26].[F-].[Cs+]>Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([OH:22])[C:25]([F:28])([F:27])[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@H:21]([OH:22])[C:25]([F:28])([F:27])[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 16731848(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

Product 2

HCID 16731517(2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl esterHCID 16732287(2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To 75A (1.00 g, 3.04 mmol) was added trimethyl(trifluoromethyl)silane (550 mg, 3.87 mmol) and cesium fluoride (10 mg, dried under high vacuum at 130° C. for 12 h). The mixture was stirred at rt for 24 h, and then was heated to 50° C. for 5 h. After cooling to rt, 4N HCl (ca. 10 mL) was added and the reaction was stirred overnight. The product was extracted with EtOAc (3×30 mL). The organic layer was washed with saturated aqueous NaHCO3 and brine, then dried (MgSO4), filtered and concentrated. The residue was purified via flash chromatography eluting with 0-15% ethyl acetate/hexane to provide (2R,3S)-3-(tert-butyl-dimethyl-silanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (75B) (357 mg) as a colorless oil and (2R,3S)-3-(tert-butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester (75C) (380 mg) as a white solid.

Workup

  1. temperaturewas heated to 50° C. for 5 h
  2. temperatureAfter cooling to rt
  3. stirringthe reaction was stirred overnight
  4. extractionThe product was extracted with EtOAc (3×30 mL)
  5. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified via flash chromatography
  10. washeluting with 0-15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-73116605375d4b4c9e1ef018c4f03d1a
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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