Water → HCID 17989118, compound

HRID 1443245Notes

Reaction equation

HRID 1443245 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5](=[O:19])[CH2:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=2[O:17][CH3:18])[CH2:9][CH2:8]1)[CH3:2].[F:21][C:22]([Si](C)(C)C)([F:24])[F:23].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:20])[C:5]([OH:19])([C:22]([F:24])([F:23])[F:21])[CH2:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=2[O:17][CH3:18])[CH2:9][CH2:8]1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 17989266HCID 17989266, compound

Product 1

HCID 17989118HCID 17989118, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

9.6 g (34.3 mmol) of ethyl-3-[1-(3-fluoro-2-methoxyphenyl)-cyclopropyl]-2-oxopropionate and 34.5 ml (233 mmol) of (trifluoromethyl)-trimethylsilane in 343 ml of DMF are mixed with 46.9 g of cesium carbonate at 0° C. It is stirred for 2 hours at 0° C. and then the reaction solution 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%), 10.4 g 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 297 ml of diethyl ether at 0° C. with 2.25 g (59.4 mmol) of lithium aluminum hydride and stirred for one more hour 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 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%-50%), 5.6 g of 3-[1-(3-fluoro-2-methoxyphenyl)-cyclopropyl]-2-(trifluoromethyl)-propane-1,2-diol is obtained. 12.4 ml (89 mmol) of triethylamine and, in portions over 10 minutes, 11 g (70 mmol) of pyridine/SO3 complex are added to 5.6 g (18.1 mmol) of diol in 100 ml of dichloromethane and 61 ml of DMSO. It is stirred over 3 hours, and saturated ammonium chloride solution is added. The mixture is stirred for another 15 minutes, the phases are separated, and it is extracted with dichloromethane. It is washed with water and dried on sodium sulfate. The solvent is removed in a vacuum, and after chromatographic purification on silica gel (hexane/ethyl acetate, 0-50%), 5.9 g of product is obtained.

Workup

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

Sources & evidence

ORD record
ord-0eb83b48c5cf41e0967b8202c59f4160
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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