Dichloromethane → tert-Butyl 2-(5-(2,3-difluoro-4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Participants

Reaction Steps

A suspension of tert-butyl 2-(5-(4-(benzyloxy)-2,3-difluorophenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (169 mg, 0.32 mmol) in a 1:3 mixture of MeOH:EtOAc (12 mL) was added to a nitrogen flushed flask containing 10% Pd/C (17 mg). The reaction mixture was placed under hydrogen atmosphere (50 psi) on a Parr shaker for 18 hours. Additional 10% Pd/C (169 mg) was added and the reaction was re-subjected to hydrogenation at 50 psi using a Parr shaker for a further 5 days. The reaction mixture was placed under an inert atmosphere (nitrogen), diluted with 10% MeOH/DCM (50 mL), filtered through celite, and rinsed with DCM. The filtrate was concentrated in vacuo to afford a pale brown solid which was re-dissolved in a 1:1 mixture MeOH:DCM (8 mL) and re-subjected to hydrogenation for 4 days at 50 psi using a Parr shaker and 10% Pd/C (169 mg) as the catalyst. The reaction mixture was diluted with 10% MeOH/DCM (50 mL), filtered through celite, and rinsed with DCM. The filtrate was concentrated in vacuo to afford the crude product as a slightly off-white solid. The crude material was purified by flash chromatography using a 12 g silica cartridge running a MeOH/DCM gradient to afford the title compound as an off-white solid (47 mg, 34% yield). LC-MS: Rt 1.27 min; MS m/z 439.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.65 (td, J=8.5, 2.2 Hz, 1H), 6.92 (td, J=8.5, 1.9 Hz, 1H), 3.87 (s, 4H), 3.20-3.31 (m, 4H), 1.67-1.78 (m, 4H), 1.40 (s, 9H).

Provenance & Evidence