Water → HCID 17989118, compound

HRID 1362492Notes

Reaction equation

HRID 1362492 reaction equation
[F:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([C:8]2([CH2:11][C:12](=[O:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[F:21][C:22]([Si](C)(C)C)([F:24])[F:23].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[F:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([C:8]2([CH2:11][C:12]([OH:18])([C:22]([F:24])([F:23])[F:21])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

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 admixed with 46.9 g of caesium carbonate at 0° C. The reaction mixture is stirred at 0° C. for 2 h and then poured into water. It is extracted repeatedly with ethyl acetate and the extracts are washed with saturated sodium chloride solution, dried with sodium sulphate and concentrated in vacuo. Purification by chromatography on silica gel (hexane/ethyl acetate 10%-40%) affords 10.4 g of ethyl 3-[1-(3-fluoro-2-methoxyphenyl)-cyclopropyl]-2-hydroxy-2-(trifluoromethyl)propanoate as a yellow oil. This oil, in 297 ml of diethyl ether, is admixed at 0° C. with 2.25 g (59.4 mmol) of lithium aluminum hydride and the mixture is stirred at RT for a further hour. 20 ml of saturated ammonium chloride solution are added cautiously to the batch at 0° C., followed by 15 minutes of vigorous stirring. The mixture is extracted repeatedly with diethyl ether and the extracts are washed with saturated sodium chloride solution, dried with sodium sulphate and concentrated in vacuo. Purification by chromatography on silica gel (hexane/ethyl acetate 10%-50%) affords 5.6 g of 3-[1-(3-fluoro-2-methoxyphenyl)cyclopropyl]-2-(trifluoromethyl)propane-1,2-diol. 5.6 g (18.1 mmol) of diol in 100 ml of dichloromethane and 61 ml of DMSO are admixed with 12.4 ml (89 mmol) of triethylamine and over 10 minutes with 11 g (70 mmol) of pyridine SO3 complex in portions. The mixture is stirred for 3 hours and saturated ammonium chloride solution is added. The mixture is stirred for a further 15 minutes and the phases are separated and subjected to extraction with dichloromethane. The extracts are washed with water and dried over sodium sulphate. The solvent is removed in vacuo, and purification by chromatography on silica gel (hexane/ethyl acetate, 0-50%) affords 5.9 g of product.

Workup

  1. extractionIt is extracted repeatedly with ethyl acetate
  2. washthe extracts are washed with saturated sodium chloride solution
  3. dry with materialdried with sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography on silica gel (hexane/ethyl acetate 10%-40%)

Sources & evidence

ORD record
ord-2dd743838c6645e7883818c9a715685c
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

Loading…