Carbamic acid,(3,4-difluorophenyl)-, ethyl ester (9CI) synthesis

Yield:2145-85-9 95%

Reaction Conditions:

with pyridine in tetrahydrofuran at 20; for 0.5 h;

Steps:

19.A

A.. (3,4-Difluoro-phenyl)-carbamic acid ethyl esterTo a solution of 3,4-difluoro-phenylamine (1.0 g, 7.45 mmol) and pyridine (751 μL, 9.29 mmol) in THF (10 mL) is added ethyl chloroformate (888 μL, 9.29 mmol) dropwise over a 30s period. This mixture is stirred at rt for 30 min. The reaction mixture is partitioned between H₂O and EtOAc. The two layers are separated, and the organic layer is washed with HCI (1 M), H₂O, and brine, dried over MgSO₄, filtered, and concentrated in vacuo to yield 1.43 g (95%) of the product as a brown solid. ¹H NMR (CDCI₃): δ 7.45-7.35 (m, 1 H), 7.07 (q, J = 8.9 Hz,1 H), 7.00-6.90 (m, 1 H), 6.55 (br s, 1 H), 4.23 (q, J = 7.1 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H); ¹⁹ F NMR (CDCI₃): δ -135.33 (m, 1 F), -143.85 (br m, 1 F); MS 243 (M+CH₃CN+1 , 100%), 202 (M+1 ).

References:

WO2011/22449,2011,A1 Location in patent:Page/Page column 99