Hydrochloric Acid → HCID 17989118, compound

HRID 1443242Notes

Reaction equation

HRID 1443242 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5](=[O:22])[CH2:6][C:7]1([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[O:20][CH3:21])[CH2:12][CH2:11]CCC1)[CH3:2].[F:24][C:25]([Si](C)(C)C)([F:27])[F:26].[F-].C[N+](C)(C)C.Cl>C1COCC1.O>[CH2:1]([O:3][C:4](=[O:23])[C:5]([OH:22])([C:25]([F:27])([F:26])[F:24])[CH2:6][C:7]1([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[O:20][CH3:21])[CH2:12][CH2:11]1)[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 67803Tetramethylammonium fluoride2×HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 17989245HCID 17989245, compound

Product 1

HCID 17989118HCID 17989118, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

1.05 g (3.3 mmol) of ethyl-3-[1-(3-fluoro-2-methoxyphenyl)-cyclohexyl]-2-oxopropionate and 0.74 ml (5 mmol) of (trifluoromethyl)-trimethylsilane in 7 ml of THF are mixed with 62 mg of tetramethylammonium fluoride at −40° C. It is stirred for 2 hours at −25° C., and then another 0.35 ml (2.4 mmol) of (trifluoromethyl)-trimethylsilane and 62 mg of tetramethylammonium fluoride are added. After another 2 hours, 1 ml of 2N hydrochloric acid is added, and the reaction mixture is added to water. It is extracted several times with ethyl acetate, washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated by evaporation in a vacuum. After chromatographic purification on silica gel (hexane/ethyl acetate 10%-40%), 800 mg of ethyl-3-[1-(3-fluoro-2-methoxyphenyl)-cyclopropyl]-2-hydroxy-2-(trifluoromethyl)-propionate is obtained as a yellow oil. This oil is mixed in 40 ml of diethyl ether at 0° C. with 150 g (4 mmol) of lithium aluminum hydride and stirred for 2.5 more hours at room temperature. 20 ml of saturated ammonium chloride solution is carefully added to the batch at 0° C., and it is stirred vigorously for 15 minutes. It is extracted several times with diethyl ether, washed with saturated sodium chloride solution, dried with sodium sulfate, and concentrated by evaporation in a vacuum. After chromatographic purification on silica gel (hexane/ethyl acetate 10%-15%), 630 g of 3-[1-(3-fluoro-2-methoxyphenyl)-cyclopropyl]-2-(trifluoromethyl)-propane-1,2-diol is obtained.

Workup

  1. waitAfter another 2 hours
  2. extractionIt is extracted several times with ethyl acetate
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated by evaporation in a vacuum
  6. customAfter chromatographic purification on silica gel (hexane/ethyl acetate 10%-40%)

Sources & evidence

ORD record
ord-9ec6f2e13ceb46cd8863bf0e6ba36ad3
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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