Aluminium lithium hydride → isopropyl 3,5-difluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate

HRID 1179481Notes

Reaction equation

[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:13]=[C:12]([NH:14][C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:11]=[C:10]([F:21])[C:9]=1/[CH:22]=[CH:23]/[C:24](OC)=[O:25]>C1COCC1>[F:7][C:8]1[CH:13]=[C:12]([NH:14][C:15](=[O:16])[O:17][CH:18]([CH3:19])[CH3:20])[CH:11]=[C:10]([F:21])[C:9]=1/[CH:22]=[CH:23]/[CH2:24][OH:25]

Participants

Conditions

Temperature: -20 °C

Procedure

A solution of LiAlH4 (26 mL of a 1.0 M THF solution, 26 mmol) was added to a cooled (−78° C.) solution of methyl (2E)-3-{2,6-difluoro-4-[(isopropoxycarbonyl)amino]phenyl}acrylate (7.77 g, 26 mmol) in THF (130 mL). The solution was allowed to warm slowly to −20° C. and maintained at that temperature for 2 hours. The reaction mixture was then quenched by slow addition of saturated NH4Cl and then treated with 30 mL of dilute citric acid. The resulting mixture was stirred for 15 minutes and then extracted with three portions of ethyl acetate. Combined organic phases were washed with H2O, brine and dried (MgSO4), filtered and concentrated to give a red oil. The crude product was purified by column chromatography (0-1% methanol-dichloromethane) to afford the title compound as a yellow oil.

Workup

temperaturemaintained at that temperature for 2 hours
customThe reaction mixture was then quenched by slow addition of saturated NH4Cl
additiontreated with 30 mL of dilute citric acid
extractionextracted with three portions of ethyl acetate
washCombined organic phases were washed with H2O, brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customto give a red oil
customThe crude product was purified by column chromatography (0-1% methanol-dichloromethane)

Sources & evidence

ORD record: ord-4a606c4960364068bd452fe3add2d146
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07279494B2

Reaction notes

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