Diethyl dimethylmalonate → 3-(4-Benzyloxy-phenyl)-2,2-dimethyl-3-oxo-propionic acid ethyl ester

HRID 2212558

Reaction equation

C([Li])(CC)C.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1.[CH3:21][C:22]([CH3:33])([C:28](OCC)=[O:29])[C:23]([O:25][CH2:26][CH3:27])=[O:24]>C1COCC1>[CH2:26]([O:25][C:23](=[O:24])[C:22]([CH3:33])([CH3:21])[C:28]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)=[O:29])[CH3:27]

Participants

Conditions

Temperature: -78 °C

Procedure

sec-Butyl lithium (5.85 mL, 7.6 mmol) was added to a solution of 1-bromo-4-benzyloxy-benzene (2.0 g, 7.6 mmol) in THF (10 mL) cooled to −78° C. under nitrogen. The reaction was stirred for 1 h and diethyl dimethylmalonate (4.29 g, 22.8 mmol) was added rapidly. This was stirred for an additional 0.5 h and then allowed to warm to room temperature. The reaction was partitioned between ethyl acetate and 1 N HCl. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give an oil. The product was purified by flash column chromatography (FCC) on silica gel eluting hexane:ethyl acetate (90: 10, v:v) to give 3-(4-benzyloxy-phenyl)-2,2-dimethyl-3-oxo-propionic acid ethyl ester (1.25 g, 50%) as an oil. MS found: (M+H)+=327.

Workup

stirringThis was stirred for an additional 0.5 h
temperatureto warm to room temperature
customThe reaction was partitioned between ethyl acetate and 1 N HCl
washThe organic layer was washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customto give an oil
customThe product was purified by flash column chromatography (FCC) on silica gel
washeluting hexane:ethyl acetate (90: 10, v:v)

Sources & evidence

ORD record: ord-5359d81de4724a08af69adbf01961d95
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07102008B2

Linked notes

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