Potassium bisulfate → (4R)-4-{[6-(Benzyloxy)pyridin-2-yl]oxy}-1-(tert-butoxycarbonyl)-L-proline

Participants

Reaction Steps

A 500 mL 3-neck round bottom flask under nitrogen was charged with Boc-L-4-hydroxyproline (Chem Impex) (2.00 g, 8.65 mmol) and DMSO (80 ml). Attached an addition funnel containing a solution of the product of Step 1 (1.758 g, 8.65 mmol) in DMSO (10 ml). Cooled reaction in an ice bath to +18° C. Added potassium-t-butoxide (2.91 g, 25.9 mmol) slowly keeping the internal temperature<20° C. Stirred 45 minutes at room temperature. Cooled to 15° C. Added contents of addition funnel dropwise. Warmed to room temperature. Stirred 1.5 hours. Poured into 2.5% potassium bisulfate. Extracted three times with ethyl acetate, washed combined organic portions with water then brine, dried with anhydrous magnesium sulfate, filtered and rotary evaporated filtrate to give the title compound as a white foam. (3.58 g, 8.65 mmol, 100% yield). LCMS (ES+) m/z 415.3 (M+H)+.

Provenance & Evidence