Sodium Hydroxide → HCID 68291765, compound

Participants

Reaction Steps

1N aqueous sodium hydroxide (5.69 ml, 5.69 mmol) was added in one portion to a solution of methyl 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylate (711 mg, 2.28 mmol) in anhydrous THF (9.11 ml). The reaction was allowed to stir at room temperature for 3.5 hours before evaporating the organic in vacuo. The remaining aqueous was cooled to 0° C. and acidified to pH 4 using 1N HCl. The aqueous phase was then extracted with ethyl acetate (3×25 mL). The aqueous pH was re-checked and judged to be ˜pH 6-7. A small amount of 1N HCl was added to re-acidify the aqueous layer which was once again extracted with an additional portion of ethyl acetate (1×25 mL). The combined organics were dried (MgSO4) and evaporated in vacuo to give crude 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylic acid (679 mg, 2.28 mmol, 100% yield) as a white solid which was used immediately in the next reaction. EDC (545 mg, 2.84 mmol) was added in one portion to a mixture of 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylic acid (679 mg, 2.28 mmol) and HOBT (436 mg, 2.84 mmol) in anhydrous dichloromethane (23.0 ml) and the reaction allowed to stir at room temperature under a nitrogen atmosphere for 30 minutes. Ammonia was then bubbled through for approximately 5 minutes and the resulting white suspension allowed to stir at room temperature overnight. The reaction was then evaporated in vacuo and the residue partitioned between ethyl acetate (25 mL) and water (25 mL). The organic layer was then dried (MgSO4) and evaporated in vacuo to give tert-butyl-((2R,3R)-3-(4-carbamoyloxazol-2-yl)pentan-2-yl)carbamate (677 mg, 2.28 mmol, 100% yield) which was used immediately in the next step. LC/MS: M+H+320.15, ret. time=1.89 min. Column: Phenomenex, 2.0×30 mm, 2.5-μm particles; Mobile Phase A: 10:90 methanol:water with 0.05% TFA; Mobile Phase B: 90:10 methanol:water with 0.05% TFA; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min. HPLC: ret. time=2.73 min. Column: YMC CombiScreen ODS-A, 4.6×50 mm; Mobile Phase A: 10:90 methanol:water with 0.2% H3PO4; Mobile Phase B: 90:10 methanol:water with 0.2% H3PO4; Temperature: 50° C.; Gradient: 0-100% B over 4 minutes, then a 0.75-minute hold at 100% B; Flow: 4 mL/min.

Provenance & Evidence