Ethyl Acetoacetate → Methyl 4-(2-(ethoxycarbonyl)-3-oxobutyl)-3-methoxybenzoate

HRID 1617151Notes

Reaction equation

[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].Br[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[O:24][CH3:25]>C1COCC1>[CH2:10]([O:9][C:3]([CH:4]([C:5](=[O:6])[CH3:7])[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[O:24][CH3:25])=[O:8])[CH3:11]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (60% in mineral oil; 1.45 g) was added portionwise over 10 min to a solution of ethyl acetoacetate (4.4 mL) in THF (60 mL) at 0° C. The resulting suspension was stirred at 0° C. for 10 min and a solution of methyl 4-(bromomethyl)-3-methoxybenzoate (7.5 g) in THF (40 mL) added portionwise over 10 min. The mixture was warmed to 70° C. and stirred for 15 h. The mixture was allowed to cool and then poured cautiously into ice/water (300 mL) and stirred for 30 min. The aqueous phase was extracted with EtOAc and the combined organic phase was dried filtered and evaporated to afford crude product. The reaction was repeated on an identical scale and the two batches of crude product were combined and purified by chromatography eluting with 20-30% EtOAc in isohexane to give the subtitle compound as a colorless oil 14.70 g.

Workup

temperatureThe mixture was warmed to 70° C.
stirringstirred for 15 h
temperatureto cool
stirringstirred for 30 min
extractionThe aqueous phase was extracted with EtOAc
customthe combined organic phase was dried
filtrationfiltered
customevaporated
customto afford crude product
custompurified by chromatography
washeluting with 20-30% EtOAc in isohexane

Sources & evidence

ORD record: ord-4cfe341bdbd140e281ba695c47354776
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765939B2

Reaction notes

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