Cyclohexaneacetic acid → HCID 10097120, compound

Participants

Reaction Steps

To a room temperature solution of INTERMEDIATE 5a (250 mg; 0.54 mmol) in DMF (5 mL) was added cyclohexyl acetic acid (92 mg; 0.65 mmol), DIPEA (0.38 mL; 2.16 mmol) and HATU (0.31 g; 0.81 mmol). The reaction mixture was stirred for 22 hours then was concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with sodium hydroxide (2N) then with HCl (1M). The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and TFA (1.5 mL) was added. The reaction mixture was stirred for 4 hours then was washed with saturated sodium bicarbonate. The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. Column chromatography eluting with 5% methanol in dichloromethane gave COMPOUND 77 (242 g; 92% for two steps). Purity (HPLC-215 nm): >99%; Optical purity (Chiral HPLC-215 nm): >99%. 1H NMR (400 MHz, CD3OD) δ 0.87-0.93 (m, 2H), 0.98 (t, J=7.13 Hz, 3H), 1.08-1.14 (m, 3H), 1.20-1.23 (m, 2H), 1.52-1.71 (br s, 6H), 1.72-1.77 (m, 1H), 2.12 (d, J=7.03 Hz, 2H), 3.09-3.14 (m, 2H), 3.18-3.23 (m, 6H), 3.26-3.33 (br s, 3H), 3.48-3.52 (m, 1H), 5.08 (s, 1H), 7.20 (d, J=4.49 Hz, 2H), 7.24-7.31 (m, 3H), 7.57 (d, J=7.81 Hz, 2H), 7.83 (s, 1H). Found: C, 58.11; H, 8.99; N, 7.46. C30H42N4O2×0.4HCl×6.5H2O has C, 57.90; H, 8.97; N, 9.00%. [α]D17=+4.6 deg [c 0.46, MeOH].

Provenance & Evidence