Sodium hydride → 4-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenoxymethyl}-benzoic acid ethyl ester

HRID 1095926Notes

Reaction equation

HRID 1095926 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:23])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([OH:21])([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=1)[C:10]([F:13])([F:12])[F:11].[H-].[Na+].[CH2:26]([O:28][C:29](=[O:38])[C:30]1[CH:35]=[CH:34][C:33]([CH2:36]Br)=[CH:32][CH:31]=1)[CH3:27]>CN(C=O)C>[CH2:26]([O:28][C:29](=[O:38])[C:30]1[CH:35]=[CH:34][C:33]([CH2:36][O:23][C:4]2[CH:5]=[CH:6][C:7]([CH:8]([CH3:22])[C:9]([OH:21])([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=3)[C:10]([F:13])([F:11])[F:12])=[C:2]([Cl:1])[CH:3]=2)=[CH:32][CH:31]=1)[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 954261Ethyl 4-(bromomethyl)benzoateHCID 252541463-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol

Product 1

HCID 469406434-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenoxymethyl}-benzoic acid ethyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol (800 mg) in DMF (10 mL) was added to a suspension of NaH (60% in mineral oil, 204 mg) in DMF (8 mL) over a period of 20 minutes. Stirring was continued for 30 minutes at r.t. The mixture was cooled to 0° C. and ethyl-4-(bromomethyl)-benzoate (591 mg, [CAS Reg. No. 26496-94-6]) dissolved in DMF (7 mL) was added dropwise over a period of 15 minutes. Stirring was continued for 1 hour at r.t. The reaction mixture was poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a colorless foam (625 mg, 53%). MS (m/e)=508.0 [MH+].

Workup

  1. additionwas added dropwise over a period of 15 minutes
  2. stirringStirring
  3. waitwas continued for 1 hour at r.t
  4. extractionextracted two times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-0b893ec1bffe470fb7b124010fea11a4
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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