Triethylamine → 2-(4-bromo-2-fluorophenyl)-N-(2,5-difluorophenyl)acetamide

HRID 1050102Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([F:12])[CH:3]=1.[F:13][C:14]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:15]=1[NH2:16].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:16][C:15]2[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:14]=2[F:13])=[O:11])=[C:4]([F:12])[CH:3]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of 2-(4-bromo-2-fluorophenyl)acetic acid (180 mg, 0.775 mmol) and 2,5-difluoroaniline (100 mg, 0.775 mmol) in DCM (20 mL) was added Et3N (0.324 mL, 2.324 mmol) and HATU (884 mg, 2.324 mmol) in portions. Then the mixture was stirred at 20° C. for 3 h. After LCMS analysis showed the starting material had disappeared, the solvent was removed in vacuo. Then the crude product was dissolved in DCM and washed with H2O and brine. The organic layer was evaporated to dryness. The crude product which was purified by silica column chromatography (PE/EA 100/1 to 10/1) to afford 2-(4-bromo-2-fluorophenyl)-N-(2,5-difluorophenyl)acetamide (103 mg, 0.276 mmol, 35.6% yield). 1H NMR: (400 MHz, CD3OD) δ 7.87-7.82 (m, 1H), 7.39-7.26 (m, 3H), 7.20-7.13 (m, 1H), 6.90-6.82 (m, 1H), 3.83 (s, 2H); ES-LCMS: m/z 343.9 (M+H).

Workup

customthe solvent was removed in vacuo
dissolutionThen the crude product was dissolved in DCM
washwashed with H2O and brine
customThe organic layer was evaporated to dryness
customThe crude product which was purified by silica column chromatography (PE/EA 100/1 to 10/1)

Sources & evidence

ORD record: ord-08f333e3d7d145c6a940121e5afaf5ee
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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