Tetrahydrofuran → 1-[4-Fluoro-2-(2-fluoro-phenylamino)-phenyl]-propan-1-one

HRID 1887810Notes

Reaction equation

[F:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH:3]=1.[CH2:22]1COC[CH2:23]1.C([Mg]Br)C>C(OCC)(=O)C>[F:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](=[O:7])[CH2:22][CH3:23])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

In a 500 mL round bottom flask, 4-fluoro-2-(2-fluoro-phenylamino)-N-methoxy-N-methyl-benzamide (6.0 g, 20.5 mmol) was added to THF (60 mL) to give a colorless solution. The reaction was cooled to 0° C. in an ice bath and ethyl magnesium bromide (3.0 M in THF, 27.4 mL, 82.2 mmol) was added slowly over a 15 min. period. The mixture was stirred at 0° C. for 4 hr. The reaction mixture was poured into ethyl acetate (250 mL) and washed with 1N HCl (1×150 mL), water (2×150 mL) and brine (2×150 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuum. The crude material was purified by flash chromatography using 20% ethyl acetate-hexanes to give 1-[4-fluoro-2-(2-fluoro-phenylamino)-phenyl]-propan-1-one (3.0 g, 56%).

Workup

customto give a colorless solution
washwashed with 1N HCl (1×150 mL), water (2×150 mL) and brine (2×150 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuum
customThe crude material was purified by flash chromatography

Sources & evidence

ORD record: ord-2acf0f964ba04cb6b9b75807f7438ef7
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501732B2

Reaction notes

Loading…