Triethylamine → Benzenemethanol, 4-chloro-alpha-((((1,1-dimethylethyl)dimethylsilyl)oxy)methyl)-3-fluoro-, 1-methanesulfonate, (alphaR)-

HRID 1774145Notes

Reaction equation

HRID 1774145 reaction equation
C(N(CC)CC)C.[Si:8]([O:15][CH2:16][C@@H:17]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([F:26])[CH:20]=1)[OH:18])([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl>[CH3:27][S:28]([O:18][C@H:17]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([F:26])[CH:20]=1)[CH2:16][O:15][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])(=[O:30])=[O:29]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86696647(R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethanol

Product 1

HCID 71726881Benzenemethanol, 4-chloro-alpha-((((1,1-dimethylethyl)dimethylsilyl)oxy)methyl)-3-fluoro-, 1-methanesulfonate, (alphaR)-Yield 99.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (2.09 mL, 15.0 mmol) was added to a cold (0° C.) solution of (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanol (3.05 g, 10.0 mmol) in DCM (100 mL), followed by methanesulfonyl chloride (0.929 mL, 12.0 mmol). The reaction mixture was stirred at 0° C. for 30 minutes and then quenched with water (50 mL). The layers were separated, and the organic layer was washed with saturated NaHCO3, dried, filtered and concentrated to give the crude product. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (25:1) to give (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate (3.80 g, 99%) as an oil. 1H NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.20 (m, 1H), 7.12 (m, 1H), 5.50 (m, 1H), 3.91 (m, 1H), 3.80 (m, 1H), 2.98 (s, 3H), 0.88 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H).

Workup

  1. customquenched with water (50 mL)
  2. customThe layers were separated
  3. washthe organic layer was washed with saturated NaHCO3
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe crude product was purified via column chromatography
  9. washeluting with hexanes/ethyl acetate (25:1)

Sources & evidence

ORD record
ord-8c7c156ab2ad41c9a808572b55a3ab7d
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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