4-Methylmorpholine → HCID 11074788, compound

To a solution of 1-(tert-butyldimethylsilyl)-4-oxoazetidine-2(R)-carboxylic acid (15.0 g, 65.40 mmol) in THF (367 mL) at 0°, was added N-methylmorpholine (7.2 mL, 65.40 mmol) and isobutyl chloroformate (8.5 mL, 65.40 mmol). After stirring for 1.5 h at 0°, a solution of NaBH4 (9.9 g, 261.61 mmol) in H2O (98 mL) was added portion wise. The reaction was stirred 45 min, then diluted with EtOAc and quenched with aqueous HCl solution (10%) to pH 5-6. The organic phase was collected and the aqueous phase was extracted twice with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The residual oil was purified by flash chromatography (SiO2, gradient 25% to 50% EtOAc/hexane) to provide 1-(tert-butyldimethylsilyl)-4(R)-(hydroxymethyl)azetidin-2-one (8.46 g, 60% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 3.74-3.69 (m, 1H), 3.65-3.56 (m, 2H), 3.1-2.98 (m, 1H), 2.81-2.76 (m, 1H), 2.01 (s, 1H), 0.89 (s, 9H), 0.18 (s, 3H), 0.16 (s, 3H). FAB MS m/z 216.2 (MH+).

1. stirringThe reaction was stirred 45 min
2. customquenched with aqueous HCl solution (10%) to pH 5-6
3. customThe organic phase was collected
4. extractionthe aqueous phase was extracted twice with EtOAc
5. washThe combined organic layers were washed with saturated aqueous NaHCO3 and brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residual oil was purified by flash chromatography (SiO2, gradient 25% to 50% EtOAc/hexane)

ORD record

ord-6f216802e7714e31bda9f6f7170ddf3c

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211170B1