Water → HCID 53958027, compound

Participants

Reaction Steps

Pyridine (33 mL, 403 mmol) and N,N-dimethylaminopyridine (100 mg) were added to a solution of isopropyl (R)-6-amino-chroman-2-carboxylate (Example 156; 40 g, 161 mmol) and 4-[4-(3-cyclohexyl-propyl)-5-oxo-4,5-dihydro-tetrazol-1-yl]-benzenesulfonyl chloride (Example 157; 62 g, 161 mmol) in tetrahydrofuran (1 L). The reaction mixture was heated to reflux for 12 hours. The mixture was cooled to room temperature and water (200 mL) and ethyl acetate (500 mL) were added. The organic phase was washed with 1 N HCl (3×) followed by brine. The organic phase was dried (sodium sulfate) and concentrated in vacuo. The crude product was chromatographed through a short pad of silica gel (50:50 ethyl acetate/hexane). The resulting solid was mixed with hexane/diethyl ether (90:10) and the mixture filtered to afford a light yellow solid (87 g, 90%). 1H NMR (CDCl3, 300 MHz) δ 8.12 (d, 8.8 Hz, 2 H), 7.80 (d, 8.8 Hz, 2 H), 6.84 (d, 2.6 Hz, 1 H), 6.74 (m, 1 H), 6.66 (m, 1 H), 6.24 (s, 1 H), 4.71 (m, 1 H), 4.0-3.9 (m, 4 H), 2.69 (m, 2 H), 2.18 (m, 2 H), 1.88 (m, 3 H), 1.66 (m, 5 H), 1.22 (m, 6 H), 0.86 (m, 7.0 Hz, 8 H); MS (FAB) m/z 598 (MH+); Rf =0.76 (C).

Provenance & Evidence