Acetic Anhydride → Phenylmethyl 4-acetyl-2-morpholinecarboxylate

Phenylmethyl 2-morpholinecarboxylate (450 mg, 2.034 mmol) was dissolved in dichloromethane (30 ml). DIPEA (0.71 ml, 4.07 mmol) and acetic anhydride (0.23 ml, 2.441 mmol) were added and the mixture was stirred under nitrogen at room temperature for 18 hr. The solvent was removed in vacuo, the residue was portioned between dichloromethane (20 ml) and water (20 ml) and separated by hydrophobic frit. The aqueous layer was washed with dichloromethane (2×10 ml) and to the combined organic phases was added saturated sodium bicarbonate solution (20 ml). The phases were separated by hydrophobic frit and the aqueous layer was washed with dichloromethane (2×10 ml). The solvent was removed in vacuo, the residue was dissolved in dichloromethane (˜5 ml) and the residue was purified by flash chromatography (20 g silica, gradient elution, 0-100% EtOAc-Cyclohexane then 0-20% MeOH). The solvent was removed in vacuo to give the title compound (313 mg, 1.19 mmol) as a colourless oil.

1. customThe solvent was removed in vacuo
2. customseparated by hydrophobic frit
3. washThe aqueous layer was washed with dichloromethane (2×10 ml) and to the combined organic phases
4. additionwas added saturated sodium bicarbonate solution (20 ml)
5. customThe phases were separated by hydrophobic frit
6. washthe aqueous layer was washed with dichloromethane (2×10 ml)
7. customThe solvent was removed in vacuo
8. dissolutionthe residue was dissolved in dichloromethane (˜5 ml)
9. customthe residue was purified by flash chromatography (
10. wash20 g silica, gradient elution, 0-100% EtOAc-Cyclohexane
11. customThe solvent was removed in vacuo

ORD record

ord-a6e2abfd1eaf451196d739989160331b

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536169B2