Triethylamine → Hydrochloric Acid

Temperature

-55 °C

A mixture of 1.154 g of (R)-(+)-7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazine (optical purity: 71.7% e.e., (R)), 5.21 ml of triethylamine and 5.8 ml of N,N-dimethylformamide was cooled to -60 to -50° C. under a nitrogen gas stream. To this solution was added 1.00 g of N-chlorosuccinimide (NCS) and the mixture was stirred at the same temperature for 35 minutes. Then, 047 g of sodium borohydride was added thereto and the mixture was stirred at room temperature for 20 minutes. The reaction mixture was diluted with 50 ml of ethyl acetate, washed twice with 10 ml portions of 5% aqueous citric acid solution and once with 10 ml of dilute aqueous ammonia (described hereinabove), and dried over anhydrous magnesium sulfate. The desiccant was then filtered off and the filtrate was concentrated to about 30 ml. To the concentrate was added 0.72 ml of concentrated hydrochloric acid and after cooling with ice-water, the resulting crystals were collected by filtration. The procedure gave 0.984 g of hydrochloride of the title compound (yield: 51.4%). Optical Purity: 7.6% e.e., (R), 3R:3S =1.00:0.86

1. stirringthe mixture was stirred at room temperature for 20 minutes
2. washwashed twice with 10 ml portions of 5% aqueous citric acid solution and once with 10 ml of dilute aqueous ammonia (described hereinabove)
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationThe desiccant was then filtered off
5. concentrationthe filtrate was concentrated to about 30 ml
6. additionTo the concentrate was added 0.72 ml of concentrated hydrochloric acid
7. temperatureafter cooling with ice-water
8. filtrationthe resulting crystals were collected by filtration

ORD record

ord-ab6c9a17fc0c40a081e05db94cc657ce

Source dataset

uspto-grants-1989_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04880926