Triethylamine → HCID 67282405, compound

Temperature

40 °C

To a solution of bromo-(3-bromo-phenyl)-acetic acid (27.8 g, 94.6 mmol) in dichloromethane (200 ml) was added oxalylchloride (19.8 g, 156 mmol) and a few drops of N,N-dimethylformamide at room temperature. After the mixture was stirred at 40° C. for one hour, the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (30 ml) and the solution was added to a solution of (R)-3-(1-phenylethyl amino)propan-1-ol (18.6 g, 104 mmol) and triethylamine (11.6 g, 114 mmol) in dichloromethane (312 ml) at 0° C. The mixture was stirred for 1.5 hours at 0° C. and partitioned between 0.5 N hydrochloric acid and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved into 2-propanol (312 ml) and then potassium hydroxide (11.7 g, 208 mmol) was added at 0° C. The mixture was stirred at 0° C. for 3 hours and partitioned between saturated ammonium chloride solution and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude mixture was triturated with ether. The resulting solid materials were collected by filtration and dried under reduced pressure to afford diastereomerically pure 2-(3-bromo-phenyl)-4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-3-one (diastereomer 1) as white solid (9.71 g, 25%).

1. customthe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in dichloromethane (30 ml)
3. stirringThe mixture was stirred for 1.5 hours at 0° C.
4. custompartitioned between 0.5 N hydrochloric acid and dichloromethane
5. washThe organic layer was washed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated in vacuo
8. dissolutionThe residue was dissolved into 2-propanol (312 ml)
9. stirringThe mixture was stirred at 0° C. for 3 hours
10. custompartitioned between saturated ammonium chloride solution and dichloromethane
11. washThe organic layer was washed with brine
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated in vacuo
14. customThe crude mixture was triturated with ether
15. filtrationThe resulting solid materials were collected by filtration
16. customdried under reduced pressure

ORD record

ord-5e314c230d4d4e31a4dc43f4ae14aff3

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108957B2