Sodium Formate → Methyl 4-(chlorobenzoyl)-4-hydroxybutyrate

HRID 567152Notes

Reaction equation

HRID 567152 reaction equation
Br[CH:2]([C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16])[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].C([O-])=[O:19].[Na+]>CO>[Cl:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[C:9]([CH:2]([OH:19])[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6])=[O:17]

Participants

4

Reactant 2

HCID 2723810Sodium FormateHCID 18376473Methyl 4-bromo-4-(chlorobenzoyl)butyrate

Product 1

HCID 18376491Methyl 4-(chlorobenzoyl)-4-hydroxybutyrateYield 100.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 4-bromo-4-(chlorobenzoyl)butyrate (89.5 g), sodium formate (76.2 g) and methanol (400 ml) was stirred under reflux for 12 hours. The reaction mixture was concentrated, and water was added to the resulting residue and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried (MgSO4). The solvent was evaporated to give methyl 4-(chlorobenzoyl)-4-hydroxybutyrate (72.0 g, 100%) as an oily substance. This oily substance (72.0 g) was dissolved in tetrahydrofuran (400 ml), pyridine (22.2 g) was added thereto, and thereafter phenyl chlorocarbonate (43.8 g) was dropwise added thereto with cooling with ice. After the reaction mixture was stirred at room temperature for 1 hour, water was added to the reaction mixture and then extracted with ethyl acetate. The ethyl acetate layer was washed with 2N hydrochloric acid and then with water, and dried (MgSO4). The solvent was evaporated, and the crystals thus precipitated were collected by filtration to obtain methyl 4-(4-chlorobenzoyl)-4-phenoxycarbonyloxybutyrate (61.2 g, 58%). This was recrystallized from methanol to give colorless prisms. mp 97-98° C.

Workup

  1. temperatureunder reflux for 12 hours
  2. concentrationThe reaction mixture was concentrated
  3. additionwater was added to the resulting residue
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with water
  6. dry with materialdried (MgSO4)
  7. customThe solvent was evaporated

Sources & evidence

ORD record
ord-03e8cf353e604927961f4b13dfb7391b
Source dataset
uspto-grants-2001_01
Patent number
US06177452B1

Reaction notes

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