Tri-o-tolylphosphine → (E)-Ethyl 3-(4-amino-2,5-difluorophenyl)-2-butenoate

HRID 2265096Notes

Reaction equation

Br[C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[C:11]([O:16][CH2:17][CH3:18])(=[O:15])/[CH:12]=[CH:13]/[CH3:14].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[NH2:6][C:5]1[C:4]([F:10])=[CH:3][C:2](/[C:13](/[CH3:14])=[CH:12]/[C:11]([O:16][CH2:17][CH3:18])=[O:15])=[C:8]([F:9])[CH:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-bromo-2,5-difluoroaniline (5.0 g), ethyl crotonate (4.98 ml), palladium acetate (54.0 mg), tris(2-methylphenyl)phosphine (442 mg), and triethylamine (33.4 ml) was stirred at 110° C. in a nitrogen atmosphere for 48 hours. The reaction mixture was filtered through Celite, and the filtrate was concentrated. The obtained residue was separated with ethyl acetate and water. The organic layer was washed with a saturated sodium chloride solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by column chromatography (5% ethyl acetate/n-hexane) to give Compound 10a (1.69 g, 29%) as a brown solid.

Workup

filtrationThe reaction mixture was filtered through Celite
concentrationthe filtrate was concentrated
customThe obtained residue was separated with ethyl acetate and water
washThe organic layer was washed with a saturated sodium chloride solution
dry with materialdried over anhydrous sodium sulfate
distillationThe solvent was distilled off
customthe residue was purified by column chromatography (5% ethyl acetate/n-hexane)

Sources & evidence

ORD record: ord-674295b49cb84d9abb2f0ca170725b16
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07855300B2

Reaction notes

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