1,3-Cyclopentanedione → 3-({[(1R,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-(hydroxymethyl)cyclohexyl]methyl}amino)cyclopent-2-en-1-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 0.35 g (0.65 mmol) of [(1S,2R,3R,4S)-2-(aminomethyl)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexyl]methyl acetate (from Step N) in 30 mL dry toluene was added cyclopentane-1,3-dione (0.064 g, 0.65 mmol) and a catalytic amount (˜0.5 mg) of PTSA. The resulting mixture was heated at reflux for 1 hr. The solvent was removed under vacuum and the residue was dissolved in 30 mL methanol. Sodium hydroxide (15 mL, 5 N) was added and the resulting mixture was stirred at 50° C. for 2 hr. The methanol and some of water were removed under vacuum. Water (20 mL) was added and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined extracts were washed with brine, dried over Na2SO4 and the solvent was removed under vacuum. The residue was purified by prep. TLC (9:1 ethyl acetate:hexane) to give the title compound (0.12 g). 1H-NMR (CDCl3) δ: 7.70 (1H, s), 7.18 (2H, s), 6.98 (2H, m), 6.93 (2H, m), 5.18 (0.5H, bs), 4.67 (0.5H, bs), 4.22 (1H, m), 3.78 (1H, m), 3.47 (1H, m), 3.27 (1H, m), 3.07 (1H, m), 2.95 (1H, m), 2.30 (1H, t), 2.40-2.20 (5H, m), 1.90 (1H, m), 1.80 (1H, m), 1.70-1.20 (3H, m), 1.33 (3H, d, J=6.4 Hz). MS: (MH)+ 574.1.

Provenance & Evidence