Acrolein → Ethyl 3-hydroxy-2-(4-fluoro-2-trifluoromethylbenzoylamino)pent-4-enoate

HRID 506486Notes

Reaction equation

[F:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:7])=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH:29]([CH:31]=[CH2:32])=[O:30].[NH4+].[Cl-]>C1COCC1>[OH:30][CH:29]([CH:31]=[CH2:32])[CH:9]([NH:8][C:6](=[O:7])[C:5]1[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=1[C:17]([F:18])([F:19])[F:20])[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

Conditions

Temperature: -78 °C

Procedure

At −78° C., 6.0 g (0.0205 mol) of ethyl (4-fluoro-2-trifluoromethylbenzoylamino)acetate dissolved in THF were added dropwise to 24.3 ml (0.049 mol) of a 2M lithium diisopropylamide solution in THF. After 1 h at −78° C., 1.4 g (0.025 mol) of acrolein dissolved in THF were added dropwise, and the mixture was stirred at −78° C. for 1 h. Saturated NH4Cl solution was then added, and the mixture was allowed to warm to RT. The mixture was extracted with CH2Cl2, and the combined organic phases were then washed and dried and the solvent was removed. The residue was purified chromatographically (SiO2; cyclohexane/ethyl acetate). This gave 4.7 g (66% of theory) of the title compound as a colorless solid (diastereomer mixture) which was reacted further without further purification.

Workup

additionwere added dropwise
temperatureto warm to RT
extractionThe mixture was extracted with CH2Cl2
washthe combined organic phases were then washed
customdried
customthe solvent was removed
customThe residue was purified chromatographically (SiO2; cyclohexane/ethyl acetate)
customThis gave 4.7 g (66% of theory) of the title compound as a colorless solid (diastereomer mixture) which was reacted further without further purification

Sources & evidence

ORD record: ord-68251b289f7e48d79448ee0e1ae09803
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786046B2

Reaction notes

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