Diisopropylamine → Methyl 3-(3,4-dimethoxyphenyl)-2,2-dimethyl-3-oxopropanoate

HRID 1528332Notes

Reaction equation

C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][CH:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[C:25](Cl)=[O:26]>C1COCC1>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([C:25](=[O:26])[C:14]([CH3:19])([CH3:13])[C:15]([O:17][CH3:18])=[O:16])[CH:28]=[CH:29][C:30]=1[O:31][CH3:32]

Participants

Conditions

Temperature: 0 °C

Procedure

124 ml of diisopropylamine is dissolved in 500 ml of THF under a blanket of dry nitrogen and cooled to 0° C. and 550 ml n-BuLi (1.6M in hexane) is added dropwise. Next, the mixture is cooled to minus 40° C., using an acetone/N2 bath, and 100 ml methyl 2-methylproponate is added. The resulting mixture is stirred for an additional 15 min at minus 40° C., after which 160.5 g of 3,4-dimethoxybenzoyl chloride dissolved in 750 ml of THF is added dropwise in 60 min during which the temperature is kept below −40° C. The cooling bath is removed and stirring is continued for 60 min at RT. 150 ml of 4M hydrochloric acid is added and the THF layer is separated and washed with 100 ml of water, 200 ml 1 M of sodium carbonate and 100 ml of brine, dried over MgSO4 and concentrated in vacuo.

Workup

temperatureNext, the mixture is cooled to minus 40° C.
additionis added dropwise in 60 min during which the temperature
customis kept below −40° C
customThe cooling bath is removed
stirringstirring
waitis continued for 60 min at RT
addition150 ml of 4M hydrochloric acid is added
customthe THF layer is separated
washwashed with 100 ml of water, 200 ml 1 M of sodium carbonate and 100 ml of brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b018e2441ca64e9ab355ee7d8b9f900c
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090597B2

Reaction notes

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