Water → (1R,2R)-1-((tert-Butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)propan-2-yl methanesulfonate

HRID 2075327Notes

Reaction equation

HRID 2075327 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]([OH:30])[C@H:11]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:31][S:32](Cl)(=[O:34])=[O:33].O>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:31][S:32]([O:30][C@@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[C@H:11]([NH:22][C:23]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:29])[C:12]1[CH:13]=[CH:14][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:16][CH:17]=1)(=[O:34])=[O:33]

Participants

6

Reactant 3

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 70643408tert-butyl (1R,2R)-3-(tert-butyldimethylsilyloxy)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)propylcarbamate

Product 1

HCID 57634118(1R,2R)-1-((tert-Butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)propan-2-yl methanesulfonateYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1R,2R)-3-(tert-butyldimethylsilyloxy)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)-propylcarbamate (14.50 g, 32.3 mmol) in 50 mL DCM at −15° C. were added TEA (4.57 g, 45.2 mmol), N,N-dimethylpyridin-4-amine (0.197 g, 1.61 mmol), and methanesulfonyl chloride (3.26 mL, 41.9 mmol). The mixture was allowed to warm to room temperature. Distilled water (200 mL) was added, and the aqueous phase was extracted into DCM (2×200 mL). The combined organic layers were washed with cold 5% HCl, saturated sodium bicarbonate, and water. The resulting product was then chromatographed eluting with 15% EtOAc in hexane. After removing the solvent, the product was obtained as a colorless oil (15 g, yield=88%). 1H NMR (400 MHz, CD3OD) δ ppm 0.11 (d, J=3.91 Hz, 6 H) 0.93-0.98 (m, 9 H) 1.44 (s, 9 H) 2.84 (s, 3H) 3.80-3.87 (m, 2H) 4.84-4.86 (m, 1H) 5.13 (d, J=5.28 Hz, 1H) 7.58 (d, J=8.02 Hz, 2H) 7.69 (d, J=8.22 Hz, 2H).

Workup

  1. extractionthe aqueous phase was extracted into DCM (2×200 mL)
  2. washThe combined organic layers were washed with cold 5% HCl, saturated sodium bicarbonate, and water
  3. customThe resulting product was then chromatographed
  4. washeluting with 15% EtOAc in hexane
  5. customAfter removing the solvent

Sources & evidence

ORD record
ord-dfbf6c77b2924a03acf1d8b3755fc2e0
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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