Lithium Hydroxide → tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of Na2CO3 (2 mL, 2M) was added to a solution of (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (334 mg, 1.00 mmol), 3,6-dihydro-2H-pyridine-1-tert-butoxycarbonyl-4-boronic acid, pinacol ester (340 mg, 1.10 mmol) in 1,4-dioxane (6 mL). The mixture was sparged with N2 for 2 minutes. The catalyst Pd(dppf)Cl2 (65 mg, 0.08 mmol) was added in one portion. The reaction vial was sealed and heated in microwave to 120° C. for 20 minutes. A solution of LiOH (0.7 mL, 3M) was added. The mixture was stirred at room temperature for 18 hours. Water (30 mL) was added to the mixture, extracted with DCM (3×20 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0-5% MeOH/DCM gradient elution) to give tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate as an oil (221 mg, 67%). 1H NMR (CDCl3, 400 MHz) δ 9.01 (s, 1H), 6.44 (s, 1H), 5.30 (m, 1H), 4.16-4.11 (m, 2H), 3.71-3.55 (m, 3H), 2.83-2.78 (m, 1H), 2.50-2.30 (m, 1H), 2.28-2.24 (m, 2H), 1.50 (s, 9H), 1.28-1.22 (m, 3H).

Provenance & Evidence