4-(3-broMophenyl)tetrahydro-2h-pyran-4-carboxaMide synthesis

Yield:329025-26-5 99.8%

Reaction Conditions:

with sulfuric acid at 20; for 40 h;

Steps:

1.1

Step 1: Preparation of 4-(3-bromophenyl)-tetrahydro-2H-pyran-4-carboxamide 4-(3-bromophenyl)tetrahydro-2H-pyran-4-carbonitrile made by the procedures described in EP 108114 (1.05 kg, 3.95 mole) was stirred in 98% H₂SO₄ (3.00 L) at room temperature for about 40 h. The mixture was then poured onto ice and the very fine suspension was filtered and washed with H₂O thoroughly until pH of wash is neutral. The white solid was washed with hexanes and was then dried in vacuo at 35-40° C. to give 1119 g (99.8% yield) of product in 99.9% purity. LC/MS: 5%-100% CH3CN:H20-0.01% TFA gradient over 10 minutes: 4.68 min. (M+H)⁺. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 7.50-7.49 (m, 1H), 7.43-7.40 (m, 1H), 7.36-7.30 (m, 1H), 7.27 (d, J=7.92 Hz, 1H) 7.06 (s, 1H), 5.00 (brs, 1H) 3.71 (dt, J=11.7, 3.7 Hz, 2H), 3.42 (t, J=10.7 Hz, 2H), 2.38 (d, J=13.6 Hz, 2H), 1.75 (td, J=12.2, 4.3 Hz, 2H).

References:

US2008/125474,2008,A1 Location in patent:Page/Page column 15