Sodium hydride → tert-butyl 3-oxotetrahydro-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate

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Borane-THF complex (1.0 M solution in THF, 200 mL, 200 mmol) was added slowly to a solution of 1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (30.3 g, 91.7 mmol) in THF (100 mL). Upon complete addition, the reaction mixture was heated to 50° C. for 2 h. Upon cooling to rt, the reaction mixture was carefully quenched by the dropwise addition of MeOH. After gas evolution ceased, the reaction mixture was concentrated under reduced pressure. The material was dissolved in EtOAc (300 mL) and washed with 1 N NaOH (2×200 mL) and brine (200 mL). The organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was twice dissolved in THF (50 mL) and concentrated under reduced pressure. The material was dissolved in THF (200 mL) and NaH (60% dispersion in mineral oil, 0.366 g, 0.916 mmol) was added portionwise. The reaction mixture was heated to reflux. After 1 h, the reaction mixture was allowed to cool to rt and was concentrated under reduced pressure. The material was dissolved in EtOAc (300 mL), washed with water (2×200 mL) and brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting solid was dissolved in EtOAc (200 mL) with heating, diluted with hexanes (200 mL) and allowed to cool to rt. The white, crystalline solid was collected by filtration after 5 h, washed with hexanes (2×), and dried under vacuum. This gave 13.29 g (60%) of the product. The filtrate was concentrated under reduced pressure, dissolved in EtOAc (50 mL) with heating, and diluted with hexanes (200 mL). This was allowed to cool to rt and sit over the weekend. The white, crystalline solid was collected by filtration, washed with hexanes (2×), and dried under vacuum. This gave an additional 4.49 g (20%) of the product. Analytical data: Rf=0.43 in 80% EtOAc/Hexanes; 1H NMR (400 MHz, CDCl3) δ 4.41 (t, J=8.4 Hz, 1H), 4.35-3.98 (br, 2H), 3.92 (dd, J=5.6 and 8.8 Hz, 1H), 3.80-3.72 (m, 2H), 2.98 (dt, J=3.6 and 12.4 Hz, 1H), 2.86-2.70 (br, 1H), 2.70-2.55, (br, 1H), 1.45 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 156.7, 154.2, 81.1, 65.5, 52.9, 47.7 (br), 43.4 (br), 41.1, 28.7. LC-MS: RT=6.46 min; [M+Na]+=264.9. Anal. Calcd for C11H18N2O4: C, 54.53; H, 7.49; N, 11.56. Found: C, 54.38; H, 7.44; N, 11.35.

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