Chloroacetyl chloride → 4-(4-Methoxy-benzyl)-6-methyl-[1,4]oxazepan-3-one

Temperature

0 °C

To a solution of 3-(4-methoxy-benzylamino)-2-methyl-propan-1-ol (4.14 g, 19.8 mmol) in dichloromethane (60 ml) was added triethylamine (2.20 g, 21.8 mmol) and chloroacetyl chloride (2.46 g, 21.8 mmol) at 0° C. The mixture was stirred at 0° C. for one hour and partitioned between 0.5N—HCl and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved into 2-propanol (66.7 ml), then potassium hydroxide (2.22 g, 39.6 mmol) was added at 0° C. The mixture was stirred for 16 hours and partitioned between saturated ammonium chloride aqueous solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=1/1 to 1/3) to afford 4-(4-methoxy-benzyl)-6-methyl-[1,4]oxazepan-3-one as white solid (4.35 g, 88%).

1. custompartitioned between 0.5N—HCl and dichloromethane
2. washThe organic layer was washed with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved into 2-propanol (66.7 ml)
6. stirringThe mixture was stirred for 16 hours
7. custompartitioned between saturated ammonium chloride aqueous solution and ethyl acetate
8. washThe organic layer was washed with brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated in vacuo
11. customThe residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=1/1 to 1/3)

ORD record

ord-87d1530e0b324c06b2149087b84c7854

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108957B2