Hydrochloric Acid → HCID 17989118, compound

HRID 1869423Notes

Reaction equation

HRID 1869423 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 it is stirred for 2.5 more hours at room temperature. 20 ml of saturated ammonium chloride solution is carefully added at 0° C. to the batch, and it is vigorously stirred for 15 more 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%-1 5%), 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-832e155994b341a4b7dbff71893895d5
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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