Sodium hydride → HCID 66742800, compound

Participants

Reaction Steps

As shown in step 24-iii of Scheme 24, to a solution of ditert-butyl propanedioate (3.579 g, 3.705 mL, 16.55 mmol) in THF (50 mL) at 23° C. was added NaH (496.4 mg, 12.41 mmol). After stirring for 20 minutes, a solution of Compound 2076 (2.70 g, 8.275 mmol) in THF (50 mL) was added. After 1 hour, the reaction was quenched with saturated aqueous ammonium chloride (100 mL) and partitioned between water and EtOAc (150 mL each). The organics were separated, washed with brine (200 mL) containing 1 N HCl (10 mL aq), washed with brine (150 mL), dried (magnesium sulfate), filtered and concentrated under reduced pressure. The residue was purified by medium pressure silica gel chromatography (0-100% EtOAc in hexanes) to provide intermediate tert-butyl 4′-methyl-2′,5′-dioxo-6′-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1′,2′,4,5,5′,6′-hexahydro-2H-spiro[furan-3,7′-pyrrolo[3,4-b]pyridine]-3′-carboxylate (2.03 g, 4.334 mmol) as a pale yellow solid: ESMS (M+H) 469.31; 1H NMR (DMSO-d6, 300 MHz) δ 12.80 (br s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 5.17 (q, J=9, 2 H), 4.18 (d, J=12, 1 H), 3.90 (m, 2H), 3.75 (m, 1H), 2.45 (m, 1H), 2.44 (s, 3H), 2.33 (m, 1H), 1.52 (s, 9H).

Provenance & Evidence