Diisopropylethylamine → 5-((R)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-3-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one

Participants

Reaction Steps

To a solution of (R)-2-(tert-butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (102 mg, 0.369 mmol), 3-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (50 mg, 0.184 mmol), and N,N′-diisopropylethylamine (112 mg, 0.870 mmol) in THF (5 mL) was added BOP reagent (144 mg, 0.326 mmol) and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated to dryness and the crude reaction mixture was concentrated and purified by column chromatography (12 g, SiO2, 0 to 30% ethyl acetate in hexanes). The purified fractions were re-dissolved in dichloromethane (5 mL), cooled to 0° C. and stirred with TFA (1 mL) for 5 hours at room temperature. The reaction mixture was concentrated to dryness, re-dissolved in dichloromethane (20 mL), washed with sat. NaHCO3 solution (5 mL), brine (5 mL), dried (MgSO4), and concentrated to provide 5-((R)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-3-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (55 mg, 67%) as a mixture of diastereoisomers in form of white solid: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.81-1.01 (m, 6H), 1.58-1.88 (m, 2H), 2.25-2.54 (m, 5H), 2.65-2.97 (m, 2H), 3.52 (d, J=6.40 Hz, 1H), 3.75-3.95 (m, 2H), 3.98-4.11 (m, 3H), 4.56-4.86 (m, 1H), 6.51 (s, 1H), 6.59-6.73 (m, 1H), 6.95 (t, J=8.48 Hz, 1H), 7.28-7.45 (m, 5H); MS m/z 447 (M+H)+.

Provenance & Evidence