Boron tribromide → Diethyl 2-(2,6-difluoro-4-hydroxyphenyl)malonate

HRID 1786299Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([O:8]C)[CH:5]=[C:4]([F:10])[C:3]=1[CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([F:10])[C:3]=1[CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of diethyl 2-(2,6-difluoro-4-methoxyphenyl)malonate (2.11 g, 7.0 mmol) in 60 mL of methylene chloride at −78° C. is added boron tribromide (2.65 mL, 28 mmol) dropwise. The mixture is then stirred at −78° C. for 10 minutes, warmed to 0° C., and stirred at 0° C. for 1 h. A 5% aqueous solution of sodium bicarbonate is added slowly to quench the reaction. The product is extracted with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride, dried over magnesium sulfate, and concentrated to a residue. The residue is chromatographed over silica gel, eluting with a gradient of 10% ethyl acetate in hexanes to 30% ethyl acetate in hexanes. Concentration provides diethyl 2-(2,6-difluoro-4-hydroxyphenyl)malonate as a colorless oil (1.91 g). MS: m/z 287.2 (M−H).

Workup

temperaturewarmed to 0° C.
stirringstirred at 0° C. for 1 h
customto quench
customthe reaction
extractionThe product is extracted with ethyl acetate
washThe combined organic extracts are washed with saturated sodium chloride
dry with materialdried over magnesium sulfate
concentrationconcentrated to a residue
customThe residue is chromatographed over silica gel
washeluting with a gradient of 10% ethyl acetate in hexanes to 30% ethyl acetate in hexanes
concentrationConcentration

Sources & evidence

ORD record: ord-46c8f9dfedd640ea8424108be2403a20
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07507739B2

Reaction notes

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