Citric Acid → benzyl 3-fluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate

HRID 1179489Notes

Reaction equation

[H-].C([Al+]CC(C)C)C(C)C.[CH2:11]([O:18][C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30](OC)=[O:31])=[C:24]([F:34])[CH:23]=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OCC)(=O)C>C1COCC1>[F:34][C:24]1[CH:23]=[C:22]([NH:21][C:19](=[O:20])[O:18][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:27]=[CH:26][C:25]=1/[CH:28]=[CH:29]/[CH2:30][OH:31]

Participants

Conditions

Temperature: -78 °C

Procedure

A THF solution of diisobutylaluminum hydride (522 mL of a 1.0 M solution, 522 mmol) was added to a cooled (−78° C.) solution of methyl (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)acrylate (43 g, 130 mmol) in THF (900 mL). After stirring for one hour at −78° C., additional diisobutylaluminum hydride solution was added (140 mL of a 1.0 M solution, 140 mmol). After another 30 minutes, aqueous citric acid and ethyl acetate were added and the mixture allowed to warm slowly to room temperature. The layers were separated and the aqueous phase extracted with more 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 (0-40% ethyl acetate-hexane) to provide the title compound as a yellow solid.

Workup

waitAfter another 30 minutes
temperatureto warm slowly to room temperature
customThe layers were separated
extractionthe aqueous phase extracted with more 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 (0-40% ethyl acetate-hexane)

Sources & evidence

ORD record: ord-d7949f9e021e4314ac64b1f869a1db65
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07279494B2

Reaction notes

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