Triethylamine → 3-Fluoro-2-(2-methoxy-carbonylamino-ethyl)-6-nitro-benzoic acid methyl ester

Temperature

80 °C

Included water in 2-(2-carboxy-ethyl)-3-fluoro-6-nitro-benzoic acid methyl ester (20.7 g, 76 mol) was removed twice by azeotropy with toluene, and the starting material was dissolved in dry toluene (380 mL). To this solution, diphenylphosphoryl azide (17.1 mL, 80 mmol) and triethylamine (11.6 mL, 83.6 mmol) were added at rt and the mixture was stirred at 80° C. for 2.0 hrs. Then, a solution of copper chloride (1.02 g, 7.6 mmol) in dry methanol (170 mL) was added and the resulting mixture was further stirred at 80° C. for 1.5 hrs. After cooling, saturated sodium hydrogen carbonate was added and the mixture was extracted three times with ethyl acetate. The organic layer was washed three times with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The resulting solid was washed with methanol and then ether to give 3-fluoro-2-(2-methoxy-carbonylamino-ethyl)-6-nitro-benzoic acid methyl ester (16.6 g) as pale brown solid in 72% yield. The filtrate was purified by column chromatography (hexane/ethyl acetate=from 4/1 to 1/1) to give additional title compound (3.8 g) as pale brown. As a result, total 20.4 g of 3-fluoro-2-(2-methoxycarbonylamino-ethyl)-6-nitro-benzoic acid methyl ester was obtained in 89% yield.

1. customwas removed twice by azeotropy with toluene
2. dissolutionthe starting material was dissolved in dry toluene (380 mL)
3. stirringthe resulting mixture was further stirred at 80° C. for 1.5 hrs
4. temperatureAfter cooling
5. extractionthe mixture was extracted three times with ethyl acetate
6. washThe organic layer was washed three times with water and brine
7. dry with materialdried over magnesium sulfate
8. customevaporated in vacuo
9. washThe resulting solid was washed with methanol

ORD record

ord-71689341478946dc9f22c39646f39b89

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07910585B2