2,6-Difluorobenzoic acid → 2,6-Difluorobenzoyl chloride

A mixture of 2,6-difluorobenzoic acid (10 g, 63.3 mmol) and DMF (3 drops) in dichloromethane (150 ml) was treated with thionyl chloride (23 ml, 316.5 mmol). The mixture was heated at reflux overnight. The solvent was removed in vacuo and the residue azeotroped (toluene 3×50 ml) to give 2,6-difluorobenzoyl chloride as an oil (8.59 g, 77%). N Boc-L4-aminophenylalanine methyl ester (100.92 g, 40.6 mmol) and NMM (5.3 ml, 48.7 mmol) were added to a solution of the above acid chloride in DMF (50 nm). The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate and aqueous. The aqueous layer was extracted with ethyl acetate (3×100 ml). The combined organic layers were dried (MgSO4) and evaporated in vacuo to give a pale brown oily solid. Trituration with ether gave the title compound as a white solid (6.93 g). δH(d6 DMSO) 7.67-7.53 (3H, m), 7.27-7.20 (5H, m), 4.19-4.11 (1H, m), 3.62 (3H, s), 3.00-2.73 (2H, m), 1.33 (9H, s); m/z (ESI, 70V) 457 (M++Na).

1. temperatureThe mixture was heated
2. temperatureat reflux overnight
3. customThe solvent was removed in vacuo
4. customthe residue azeotroped (toluene 3×50 ml)

ORD record

ord-0a82bd3eebf74c9f94a6f994deb1283c

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06911451B1