tert-Butanol → 2-(4-chloro-2-fluorobenzyl)-3-oxopentanoic Acid Methyl Ester

HRID 2266591Notes

Reaction equation

HRID 2266591 reaction equation
CC(C)([O-])C.[K+].C(O)(C)(C)C.[CH3:12][O:13][C:14](=[O:20])[CH2:15][C:16](=[O:19])[CH2:17][CH3:18].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[F:30]>O1CCCC1.O>[CH3:12][O:13][C:14](=[O:20])[CH:15]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[F:30])[C:16](=[O:19])[CH2:17][CH3:18]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 121699Methyl 3-oxovalerateHCID 27365514-Chloro-2-fluorobenzyl bromideHCID 23665647Potassium tert-butoxide

Product 1

HCID 687825242-(4-chloro-2-fluorobenzyl)-3-oxopentanoic Acid Methyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of potassium tert-butoxide (1.6 g) in anhydrous tetrahydrofuran (75 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid methyl ester (1.5 g). After stirring at 0° C. for 45 minutes a solution of 1-bromomethyl-4-chloro-2-fluorobenzene (2.6 g) in tetrahydrofuran (25 mL) was added and the resulting mixture stirred at room temperature for 17 hours. The mixture was diluted with water and the tetrahydrofuran removed under reduced pressure. The mixture was extracted with ethyl acetate and the combined extracts washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (1:19 to 1:9 by volume) to afford title compound, 1.4 g.

Workup

  1. additionwas added
  2. customthe tetrahydrofuran removed under reduced pressure
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined extracts washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue purified by column chromatography on silica gel
  8. washeluting with a mixture of ethyl acetate and cyclohexane (1:19 to 1:9 by volume)

Sources & evidence

ORD record
ord-bb06dbc5fb944214ad74190d3c7add86
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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