Reaction #7126

Reaction equation

(1S,2R)-2-(4-chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide

methyl 4-(bromomethyl)benzoate

cesium carbonate

→

4-[[(1R,2S)-(2-carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-benzoic acid methyl ester

Yield 22.0%

Solvents

acetonitrile

Conditions

Workup

1. 1
   FiltrationThe crude mixture was filtered through celite and
2. 2
   Concentrationconcentrated in vacuo
3. 3
   OtherThe product was purified by silica gel column chromatography (methanol/chloroform, 0.25%)

Procedure

A mixture of (1S,2R)-2-(4-chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide (670 mg, 2.12 mmol), methyl 4-(bromomethyl)benzoate (534 mg, 2.33 mmol), cesium carbonate (1.04 g, 3.18 mmol) and acetonitrile (20 mL) was stirred vigorously at room temperature for 18 h. The crude mixture was filtered through celite and concentrated in vacuo. The product was purified by silica gel column chromatography (methanol/chloroform, 0.25%) to afford 213 mg (22% yield) of 4-[[(1R,2S)-(2-carbamoyl-cyclohexyl)-(4-chlorobenzenesulfonyl)-amino]-methyl]-benzoic acid methyl ester. An analytical sample was obtained after recrystallization from ethyl acetate/hexanes: 1H NMR (400 Mz, DMSO) δ 7.85 (d, 2 H, J=8.3), 7.82 (d, 2 H, J=8.5), 7.63 (d, 2 H, J=8.5), 7.42 (d, 2 H, J=8.3), 7.28 (br s, 1 H), 6.60 (br, s, 1 H), 4.64 (ABq, 2 H, Δv=69.4, Jab=17.4), 3.88 (m, 1 H), 3.85 (s, 3 H), 2.79 (m, 1 H), 2.42 (m, 1 H), 1.78 (m, 1 H), 1.64 (m, 2 H), 1.38–1.21 (m, 3 H), 0.90 (m, 1 H); MS m/e 465.1 (M+H)+.

Source