Tert-Butylamine → 4-Bromo-N-tert-butyl-2-fluorobenzamide

HRID 911288Notes

Reaction equation

[C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Br:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[C:16]([F:23])[CH:15]=1>C(Cl)Cl>[Br:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:19])=[C:16]([F:23])[CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Combine 4-bromo-2-fluoro-benzoic acid (5.0 g, 22.83 mmol), thionyl chloride (10 mL, 0.137 mmol) in toluene (10 mL) and reflux for 2 h. Evaporate the reaction mixture to obtain 4-bromo-2-fluoro-benzoyl chloride (5.0 g, 93%) and use for the next step without further purification. Dissolve tert-butylamine (0.8 mL, 5.12 mmol) and triethylamine (0.8 mL, 6.32 mmol) in anhydrous DCM (20 mL), cool to 0° C. and add a solution of 4-bromo-2-fluoro-benzoyl chloride (1.0 g, 4.22 mmol) in anhydrous DCM (10 mL). Stir the reaction mixture at 0° C. for 10 min, warm to ambient temperature and continue to stir for 30 min. Wash the reaction mixture with brine (2×10 mL), dry the organic extracts over anhydrous Na2SO4, evaporate the solvent and purify by chromatography on silica gel eluting with DCM to obtain the desired intermediate as a white solid (1.0 g, 87%). MS (ES+) m/z: 275 (M+H)+.

Workup

customuse for the next step without further purification
temperaturewarm to ambient temperature
stirringto stir for 30 min
washWash the reaction mixture with brine (2×10 mL)
dry with materialdry the organic extracts over anhydrous Na2SO4
customevaporate the solvent
custompurify by chromatography on silica gel eluting with DCM

Sources & evidence

ORD record: ord-ba2a1e31eb2d4220b16e5fb8a4de677f
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Reaction notes

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