Hydrochloric Acid → (R)-methanesulfonic acid 1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester

HRID 918951Notes

Reaction equation

HRID 918951 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([C@H:13]([OH:15])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:18][S:19](Cl)(=[O:21])=[O:20].C(N(CC)CC)C.Cl>ClCCl.CN(C1C=CC=CN=1)C.C(Cl)(Cl)Cl>[F:1][C:2]([F:16])([F:17])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][S:19]([CH3:18])(=[O:21])=[O:20])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 2779031(alphaR)-alpha-Methyl-3,5-bis(trifluoromethyl)benzenemethanol

Product 1

HCID 89585312(R)-methanesulfonic acid 1-[3,5-bis(trifluoromethyl)phenyl]ethyl esterYield 107%

Reagents, catalysts & solvents 3

HCID 218852-DimethylaminopyridineCatalystHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

With reference to Japanese Patent No. 3938651, a solution of (R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol (optical purity, >99.5% ee; 1.6 g; 6.20 mmol) in dichloromethane (20 mL) was added with methanesulfonyl chloride (0.58 mL, 7.44 mmol), triethylamine (1.30 mL, 9.3 mmol), and dimethylaminopyridine (76 mg, 0.62 mmol) with stirring under ice cooling, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was added with 1 N hydrochloric acid and chloroform at the same temperature, and the organic layer was separated. The aqueous layer was extracted with chloroform (20 mL×3), and the organic layers were combined, washed with saturated brine, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain (R)-methanesulfonic acid 1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester (2.23 g) as colorless oil. Then, a solution of the resulting (R)-methanesulfonic acid 1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester (2.23 g) in N,N-dimethylformamide (20 mL) was added with sodium bromide (1.26 g, 12.25 mmol), and the mixture was stirred at 50° C. for 1 hour. The reaction mixture was added with water (30 mL) at room temperature, and the mixture was extracted with hexane (30 mL×3). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain 1.85 g of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane as colorless oil. On the basis of the specific rotation, it was confirmed that the resulting 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane was obtained after racemization.

Workup

  1. stirringthe mixture was stirred at the same temperature for 30 minutes
  2. customthe organic layer was separated
  3. extractionThe aqueous layer was extracted with chloroform (20 mL×3)
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5668d4d3a90c4a7c86642b8abbb7370c
Source dataset
uspto-grants-2016_03
Patent number
US09272966B2

Reaction notes

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