Cesium carbonate → 4-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxymethyl]-2-fluoro-benzoic acid methyl ester

HRID 2103435Notes

Reaction equation

HRID 2103435 reaction equation
[CH2:1]([C:5]1[N:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[S:8][C:9]=1[CH2:10][OH:11])[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:28][O:29][C:30](=[O:40])[C:31]1[CH:36]=[CH:35][C:34]([CH2:37]Br)=[CH:33][C:32]=1[F:39].[K]>CN(C=O)C>[CH3:28][O:29][C:30](=[O:40])[C:31]1[CH:36]=[CH:35][C:34]([CH2:37][O:11][CH2:10][C:9]2[S:8][C:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:21])[F:19])=[CH:14][CH:13]=3)=[N:6][C:5]=2[CH2:1][CH2:2][CH2:3][CH3:4])=[CH:33][C:32]=1[F:39]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 5462222PotassiumHCID 18759821methyl 4-(bromomethyl)-2-fluorobenzoateHCID 58934102HCID 58934102, compound

Product 1

HCID 578043094-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxymethyl]-2-fluoro-benzoic acid methyl esterYield 19.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-butyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-yl]-methanol (1.02 g, 3.24 mmol) in anhydrous DMF (150 mL) add cesium carbonate (2.7 g, 8.10 mmol) and 4-bromomethyl-2-fluoro-benzoic acid methyl ester (0.8 g, 3.24 mmol). Stir the resulting mixture overnight then pour into a 1M aqueous solution of potassium hydrogenophosphate and extracted three times with diisopropyl ether. Wash the combined extracts with water, dry over MgSO4, filter and concentrate under vacuum. Purify the residue by flash chromatography on silica gel (eluting with a gradient of heptane/ethyl acetate) to give the title compound (0.3 g) as a yellow solid.

Workup

  1. extractionextracted three times with diisopropyl ether
  2. washWash the combined extracts with water
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate under vacuum
  6. customPurify the residue by flash chromatography on silica gel (
  7. washeluting with a gradient of heptane/ethyl acetate)

Sources & evidence

ORD record
ord-46038bed66e943818aa27084f4221f5c
Source dataset
uspto-grants-2009_08
Patent number
US07576109B2

Reaction notes

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