Triethylamine → methyl 2-((2S,4R)-2-(azidomethyl)-4-(5-cyclopropylpyrazin-2-yloxy)-pyrrolidin-1-yl)acetate

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Reaction Conditions

Reaction Steps

To a solution of the product from Example 201A (290 mg, 1.114 mmol) in triethylamine (388 μl, 2.79 mmol) and methanol (0.3 mL) was added methyl bromoacetate (175 μL, 1.894 mmol), and the resulting mixture was stirred at 65° C. for 18 hours. The cooled mixture was concentrated in vacuo and partitioned between 1 N sodium bicarbonate and ethyl acetate. The organic extract was dried over Na2SO4, filtered and concentrated. The crude product was purified by 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 give the title compound as an oil (203 mg, 54.8%). 1H NMR (500 MHz, pyridine-d5) δ ppm 6.74 (s, 1H), 4.63 (s, 1H), 4.36 (d, J=61.9 Hz, 1H), 4.08 (dt, J=14.2, 6.0 Hz, 1H), 3.81 (dd, J=42.1, 9.2 Hz, 1H), 3.62 (dd, J=11.3, 4.3 Hz, 1H), 3.46-3.27 (m, 1H), 2.23 (dd, J=21.4, 10.3 Hz, 1H), 2.17-2.04 (m, 1H), 1.49 (d, J=8.4 Hz, 11H); MS (ESI) m/z 333 (M+H)+.

Provenance & Evidence