Ethanol → HCID 22962031, compound

Temperature

0 °C

At 0° C. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (7.2 g, 37.57 mmol) was added to a solution of 4′-(trifluoromethyl)-2-biphenylcarboxylic acid (10.0 g, 37.57 mmol) and 1-hydroxybenzotriazole ( 5.1 g, 37.57 mmol) in DMF (50 ml) and DCM (20 ml). The reaction mixture was stirred for 20 min at 0° C. An 8.3 M solution of methylamine in ethanol (94 ml, 751 mmol) was added. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (100 ml) and washed with a 10% aqueous solution of sodium hydrogen sulphate (100 ml). The aqueous phase was extracted with ethyl acetate (3×70 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (200 g), using ethyl acetate/heptane (2:1) as eluent, to give 8.50 g of 4′-(trifluoromethyl)biphenyl-2-carboxylic acid methylamide.

1. customAt 0° C
2. stirringThe reaction mixture was stirred for 16 hours, while it
3. temperaturewas warming up to room temperature
4. washwashed with a 10% aqueous solution of sodium hydrogen sulphate (100 ml)
5. extractionThe aqueous phase was extracted with ethyl acetate (3×70 ml)
6. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml)
7. dry with materialdried over magnesium sulphate
8. customThe solvent was removed in vacuo
9. customThe crude product was purified by flash chromatography on silica (200 g)

ORD record

ord-17c03cf083e24d9a9aeb6521f1a9062d

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06437147B1