Chloroacetyl chloride → 4-Benzyl-6-(3-methoxyphenyl)morpholin-3-one

In a 250 mL round-bottomed flask, 2-(benzylamino)-1-(3-methoxyphenyl)ethanol (1.92 g, 7.46 mmol,) and TEA (831 mg, 1.14 ml, 8.21 mmol) were combined with dichloromethane (60 ml) to give a colorless solution. To this chloroacetyl chloride (927 mg, 657 μl, 8.21 mmol) in 10 mL dichloromethane was added dropwise at 0° C. After 1 h at 0° C. the reaction mixture was quenched with 1M aqueous HCl. The layers were separated, the aqueous layer extracted with dichloromethane. The combined organic layers were washed with 5% aqueous NaHCO3, dried over Na2SO4 and concentrated in vacuo. The crude intermediate N-benzyl-2-chloro-N-[2-hydroxy-2-(3-methoxy-phenyl)-ethyl]-acetamide (2.61 g, 7.82 mmol) was combined with isopropanol (50 ml) to give a light yellow solution. KOH (526 mg, 9.38 mmol) was added and the resulting solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo. The crude product was partitioned between ethyl acetate and 0.5M aqueous HCl. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over MgSO4 and concentrated in vacuo to give 4-benzyl-6-(3-methoxyphenyl)-morpholin-3-one (2.3 g, 99%) which was directly used for next step without further purification. (M+H)+=298 m/e.

1. customto give a colorless solution
2. customAfter 1 h at 0° C. the reaction mixture was quenched with 1M aqueous HCl
3. customThe layers were separated
4. extractionthe aqueous layer extracted with dichloromethane
5. washThe combined organic layers were washed with 5% aqueous NaHCO3
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customto give a light yellow solution
9. concentrationThe reaction mixture was concentrated in vacuo
10. customThe crude product was partitioned between ethyl acetate and 0.5M aqueous HCl
11. customThe layers were separated
12. extractionthe aqueous phase was extracted with ethyl acetate
13. washThe combined ethyl acetate extracts were washed with brine
14. dry with materialdried over MgSO4
15. concentrationconcentrated in vacuo

ORD record

ord-7ccac1d304f949b4b5883ed417915398

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353096B2