Triethylamine → 2-(4-bromo-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide

HRID 576229Notes

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]([F:25])([F:24])[C:15]([C:18]1[O:22][N:21]=[C:20]([NH2:23])[CH:19]=1)([CH3:17])[CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:23][C:20]2[CH:19]=[C:18]([C:15]([CH3:17])([CH3:16])[C:14]([F:24])([F:13])[F:25])[O:22][N:21]=2)=[O:11])=[C:4]([F:12])[CH:3]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a mixture of 2-(4-bromo-2-fluorophenyl)acetic acid (100 mg, 0.429 mmol) in DCM (50 mL) was added 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine (92 mg, 0.472 mmol), HATU (245 mg, 0.644 mmol) and Et3N (0.179 mL, 1.287 mmol). Then the mixture was stirred at 25° C. for 12 h. The mixture was concentrated and the crude material was purified by preparative TLC (PE/EA=2:1, Rf=0.4) to yield a yellow oil of 2-(4-bromo-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide (50 mg, 0.109 mmol, 25.4% yield): 1H NMR (400 MHz, CDCl3) δ: 8.12 (s., 1H) 7.35-7.27 (m, 2H) 7.23-7.18 (m, 1H) 6.95 (s, 1H) 3.72 (s, 2H) 1.55 (s, 6H); ES-LCMS m/z 411 (M+2).

Workup

concentrationThe mixture was concentrated
customthe crude material was purified by preparative TLC (PE/EA=2:1, Rf=0.4)

Sources & evidence

ORD record: ord-b2c57d222d334edb81dbfb8005ec64f1
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09035063B2

Reaction notes

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