Hydrochloric Acid → HCID 71536498, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)-2-hydroxyacetate (26 mg, 0.053 mmol) was dissolved in tert butyl acetate (618 μl, 5.30 mmol), cooled to 0° C. and treated with perchloric acid (7.21 μl, 0.053 mmol) and the reaction vessel was transferred to the fridge. After 72 h (weekend), the reaction mixture was partitioned between EtOAc and sat. aq. NaHCO3 and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in THF (0.2 mL) and MeOH (0.2 mL), treated with 2M LiOH (133 μl, 0.265 mmol) and heated to 50° C. After 2 h, The reaction mixture was poured into 1M HCl and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by reverse phase HPLC to afford 2-(tert-butoxy)-2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)acetic acid (15 mg, 0.028 mmol, 53.1% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d)=7.50-7.43 (m, 1H), 7.17 (none, 5H), 7.03-6.95 (m, 2H), 5.95-5.86 (m, 1H), 5.77-5.69 (m, 1H), 5.29 (s, 1H), 4.08 (s, 1H), 3.94-3.86 (m, 1H), 3.79-3.70 (m, 1H), 3.66 (s, 3H), 3.60 (d, J=14.1 Hz, 1H), 2.70-2.53 (m, 2H), 2.42 (s, 3H), 1.05 (s, 9H). LCMS (m/z) ES+=533 (M+1).

Provenance & Evidence