Cesium carbonate → HCID 86618697, compound

Participants

Reaction Conditions

Reaction Steps

2-Bromo-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (1.0 g, 3.3 mmol, from Example 21a), tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (0.67 g, 3.3 mmol), Pd(OAc)2 (14.8 mg, 0.066 mmol), 2′-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine (28 mg, 0.083 mmol), Cs2CO3 (2.15 g, 6.6 mmol) and toluene (10 mL) were mixed, degassed and stirred at 100° C. under a nitrogen atmosphere. After 24 h, additional portions of Pd(OAc)2 (14.8 mg, 0.066 mmol) and 2′-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine (28 mg, 0.083 mmol) were added and the reaction mixture was stirred for another 24 h. H2O and DCM were added and the organic phase was separated and evaporated. The residue was purified by flash chromatography using a gradient of EtOAc/heptane to give the title compound. Yield: 604 mg (43%). 1H NMR (400 MHz, CDCl3) δ 7.56 (t, J=8.2 Hz, 1H), 7.05 (d, J=7.0 Hz, 1H), 6.58 (d, J=8.8 Hz, 1H), 4.69 (s, 2H), 4.41-4.30 (m, 1H), 4.22-4.08 (m, 2H), 3.46-3.28 (m, 2H), 2.03-1.90 (m, 3H), 1.88-1.78 (m, 1H), 1.46 (s, 9H), 0.96 (s, 9H), 0.11 (s, 6H). MS (ESI+) 445.4 (M+1Na+).

Provenance & Evidence