Imidazole → tert-butyl (1R,2R)-3-(tert-butyldimethylsilyloxy)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)propylcarbamate

HRID 661067Notes

Reaction equation

HRID 661067 reaction equation
[OH:1][C@@H:2]([CH2:22][OH:23])[C@H:3]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1.N1C=CN=C1.[Si:29](Cl)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>CN(C=O)C>[Si:29]([O:23][CH2:22][C@H:2]([OH:1])[C@H:3]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 70643409tert-butyl (1R,2R)-2,3-dihydroxy-1-(4-(trifluoromethyl)phenyl)propylcarbamate

Product 1

HCID 70643408tert-butyl (1R,2R)-3-(tert-butyldimethylsilyloxy)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)propylcarbamateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

tert-butyl (1R,2R)-2,3-dihydroxy-1-(4-(trifluoromethyl)phenyl)-propylcarbamate (11 g, 32.8 mol) in 100 mL DMF was cooled in an ice-water bath. 1H-imidazole (8.2 mL, 72 mol) was added in one portion, and the mixture was stirred for 10 minutes under nitrogen. tert-butyldimethylsilylchloride (5.43 g, 36.0 mmol) in 20 mL DMF was added via syringe. The reaction was monitored by TLC. After 16 hours, DMF was evaporated under high vacuum. 150 mL distilled water was added, and the resulting mixture was extracted into diethyl ether (2×200 mL). The ether layer was washed with saturated aqueous ammonia chloride and dried over sodium sulfate. After removing the solvent, the product was obtained as a white solid (14.0 g, yield=95%). 1H NMR (400 MHz, CD3OD) δ ppm 0.08-0.12 (m, 6H) 0.97 (s, 9H) 1.43 (s, 9H) 3.50 (s, 1H) 3.63 (s, 1H) 3.85 (s, 1H) 4.81 (s, 1H) 7.53-7.58 (m, 2H) 7.60-7.66 (m, 2H).

Workup

  1. waitAfter 16 hours
  2. customDMF was evaporated under high vacuum
  3. distillation150 mL distilled water
  4. additionwas added
  5. extractionthe resulting mixture was extracted into diethyl ether (2×200 mL)
  6. washThe ether layer was washed with saturated aqueous ammonia chloride
  7. dry with materialdried over sodium sulfate
  8. customAfter removing the solvent

Sources & evidence

ORD record
ord-73bd42e81d8744e99add8276aa2c3e83
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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