Sodium Hydroxide → (+/-)(3SR,3aRS)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

Participants

Reaction Steps

To a solution of the methyl 2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate from step 1 (3.75 g, 8.6 mmol) in methanol (10 mL) and tetrahydrofuran (30 mL) was added 10% aqueous sodium hydroxide (10 mL). The solution was stirred for 20 hours at ambient temperature. The resulting slurry was concentrated to half volume and acidified to a pH of about 2 with 1M hydrochloric acid. The resulting solid was collected by vacuum filtration to provide the title compound largely present as (±)-(3SR,3aRS)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (yellow solid, 3.79 g, quantitative yield). LC/MS on 4.6×50 mm C-18 column, tR=6.74 minutes (10 to 90% acetonitrile/water over 8 minutes at 2 mL/minute with detection 254 nm, at 50° C.); ES-MS m/z 420 (M+H); HRMS Calculated for C24H22ClN3O2: 420.1473 (M+H)+. Found: 420.1449; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-1.55 (m, 6H), 1.64-1.75 (m, 2H), 1.75-1.87 (m, 1H), 1.99-2.09 (m, 1H), 2.15-2.23 (m, 1H), 2.78-2.91 (m, 2H), 3.00 (d, J=16.11 Hz, 1H), 4.89 (dd, J=9.26, 5.77 Hz, 1H), 7.14 (dd, J=9.00, 1.75 Hz, 1H), 7.34 (d, J=1.88 Hz, 1H), 7.63 (d, J=8.86 Hz, 1H), 7.73 (s, 1H), 7.76 (s, 1H), 7.94 (d, J=7.79 Hz, 1H).

Provenance & Evidence