Ethyl Acetate → methyl(R)-2-tert-butoxycarbonylamino-6-(3,4-difluorophenyl)-6-oxohexanoate

HRID 1436123Notes

Reaction equation

[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][C:7](=[O:11])[N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:4].[F:19][C:20]1[CH:21]=[C:22]([Mg]Br)[CH:23]=[CH:24][C:25]=1[F:26].[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1>[C:15]([O:14][C:12]([NH:6][C@H:5]([CH2:10][CH2:9][CH2:8][C:7]([C:23]1[CH:22]=[CH:21][C:20]([F:19])=[C:25]([F:26])[CH:24]=1)=[O:11])[C:3]([O:2][CH3:1])=[O:4])=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of (R)-6-oxopiperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (CAS No. 183890-36-0, 5.8 g) in THF (200 mL), 3,4-difluorophenylmagnesium bromide (0.5 M solution in THF, 50 mL) was added dropwise at −40° C., and the reaction solution was stirred at −40° C. for seven hours. A saturated ammonium chloride solution and ethyl acetate were added to the reaction solution, and the mixture was heated to room temperature. Thereafter, the organic layer was separated, and the resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1) to obtain 3.8 g of the title compound. The property value of the compound is as follows.

Workup

temperaturethe mixture was heated to room temperature
customThereafter, the organic layer was separated
dry with materialthe resulting organic layer was dried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1)

Sources & evidence

ORD record: ord-b3d3a3412d374834a217a560784c503b
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618960B2

Reaction notes

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