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

HRID 2300660Notes

Reaction equation

HRID 2300660 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 2 N 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-e227f23b67564292b29513c3b4bc2a62
Source dataset
uspto-grants-2002_12
Patent number
US06498179B1

Reaction notes

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