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

HRID 1864706Notes

Reaction equation

HRID 1864706 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]

Participants

5

Reactant 2

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 16732286(2R,3R)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl esterYield 46.7%

Reagents, catalysts & solvents 2

HCID 25953Cesium fluorideCatalystHCID 313Hydrochloric AcidSolvent

Procedure

To (2S,3R)-3-(tert-butyldimethylsilanyloxy)-2-formylpyrrolidine-1-carboxylic acid tert-butyl ester (7C) (2.10 g, 6.38 mmol) was added trimethyl(trifluoromethyl)silane (800 μL, 6.57 mmol) and cesium fluoride (dried under high vacuum at 130° C. for 12 h) (10.0 mg, 0.066 mmol). The reaction was stirred at rt for 24 h then 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 brown aqueous solution was decanted and the remaining waxy yellow solid was dried under high vacuum overnight then recrystallized from hexane to provide (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxyethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (7D) (1.19 g) as a white solid. The mother liquor was concentrated and purified via flash chromatography eluting with 5-20% EtOAc/hexane to provide (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (7E) (192 mg) as an oil and a mixture of (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (7D) and starting material (306 mg). The latter was recrystallized from hexane to provide additional (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (7D) (100 mg).

Workup

  1. temperaturethen heated to 50° C. for 5 h
  2. temperatureAfter cooling to rt
  3. stirringthe reaction was stirred overnight
  4. customThe brown aqueous solution was decanted
  5. customthe remaining waxy yellow solid was dried under high vacuum overnight
  6. customthen recrystallized from hexane

Sources & evidence

ORD record
ord-2863dee096544a30a47252a518c37939
Source dataset
uspto-grants-2009_12
Patent number
US07625923B2

Reaction notes

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