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

A mixture of (1S,2R)-2-aminocyclohexanecarboxylic acid amide (16.2 mmol), 4-chlorobenzenesulfonylchloride (6.84 g, 32.4 mmol), and triethylamine (20 mL, 143 mmol) were stirred in dichloromethane/DMF (500 mL/100 mL) at room temperature for 6 h. The crude mixture was poured into 1 M hydrochloric acid (500 mL). The organic layer was collected and washed with with water (2×500 mL). Hexanes (50 mL) were added to the organic layer. The combined mixture was sequentially washed with water (500 mL) and brine (50 mL). The organic layer was dried (magnesium sulfate), filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromatography (solvent gradient: methanol/chloroform, 0.25% to 5.0%) to afford 2.73 g (53% yield, 5 steps) of (1S,2R)-2-(4-chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide. An analytical sample was obtained after recrystallization from ethyl acetate/hexanes: 1H NMR (400 MHz, DMSO-d6) 7.82 (d, 2 H, J=8.5), 7.64 (d, 2 H, J=8.6), 7.57 (d, 1 H, J=7.1), 7.22 (s, 1 H), 6.79 (s, 1 H), 3.43 (m, 1 H), 2.36 (m, 1 H), 1.72 (m, 2 H), 1.46 (m, 3 H), 1.17 (m, 3 H); MS m/e 339.1 (M+Na)+. Anal. calcd. for C13 H17ClN2O3S: C, 49.28; H, 5.40; N, 8.84. Found: C, 49.55; H, 5.24; N, 8.78. Optical rotation: [α]D=−55.8 (c=6.78 mg/mL, DMF).

1. customThe organic layer was collected
2. washwashed with with water (2×500 mL)
3. additionHexanes (50 mL) were added to the organic layer
4. washThe combined mixture was sequentially washed with water (500 mL) and brine (50 mL)
5. dry with materialThe organic layer was dried (magnesium sulfate)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by silica gel column chromatography (solvent gradient: methanol/chloroform, 0.25% to 5.0%)

ORD-Eintrag

ord-1b8b01e092bf4c23be15b02e57286005

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07084178B2