(2S,4R)-tert-butyl 2-(azidomethyl)-4-hydroxypyrrolidine-1-carboxylate → (2S,4R)-tert-butyl 2-(azidomethyl)-4-(5-cyclopropylpyrazin-2-yloxy)-pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of the product from Example 174B (98 mg, 0.404 mmol) in tetrahydrofuran (1 mL) was added potassium-t-butoxide (63.5 mg, 0.566 mmol) followed by addition of 2-bromo-5-cyclopropylpyrazine (Combi-Phos Inc; 89 mg, 0.445 mmol). After stirring at room temperature for 24 hours, the mixture was diluted with water and extracted with ethyl acetate (2×20 mL). The combined ethyl acetate extracts were dried over Na2SO4, filtered, and concentrated under a stream of nitrogen. The residue was purified by flash chromatography on a 12 g silica gel column, eluting with 5% ethyl acetate/hexanes for 3 minutes then a gradient to 100% ethyl acetate over 20 minutes to afford the title compound as a colorless oil (87 mg, 59.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (d, J=1.3 Hz, 1H), 8.06 (d, J=1.3 Hz, 1H), 5.44-5.39 (m, 1H), 4.12-4.04 (m, 1H), 3.71 (dd, J=12.4, 5.3 Hz, 1H), 3.64 (d, J=12.3 Hz, 1H), 3.57 (dd, J=12.4, 4.6 Hz, 1H), 3.39 (dd, J=12.4, 3.2 Hz, 1H), 2.30-2.06 (m, 3H), 1.41 (s, 9H), 0.97-0.90 (m, 2H), 0.87-0.81 (m, 2H).

Provenance & Evidence