(3,4-Dichlorophenyl)acetonitrile → HCID 16079683, compound

Temperature

-15 °C

To a solution of 2-(3,4-Dichlorophenyl)acetonitrile (3.5 g, 18.81 mmol) and (S)-(+)-Epichlorohydrin (1.877 ml, 23.99 mmol) in tetrahydrofuran (18.5 mL) at −15° C. (dry ice/ethanol/water bath, internal temp monitored with thermocouple) under atmosphere of N2 was added sodium bis(trimethylsilyl)amide (16.5 mL, 33.0 mmol) dropwise over 3 hours. The reaction mixture was stirred for additional 3 hours at −15° C., then, overnight at 4° C. (cold room). The mixture was cooled to −5° C. and borane-methyl sulfide complex (4.4 mL, 44.0 mmol) was added over 2 hours via syringe pump. The reaction mixture was then gradually warmed to 40° C. over 3 hours. After aging 1.5 hours at 40° C., the reaction mixture was cooled to 20-25° C. and slowly quenched into a 2N HCl solution (27.7 L). The quenched mixture was then stirred for 1 h at 40° C. Ammonium hydroxide concentrated (6.3 L) was added and the aqueous layer was discarded. i-PrOAc (18.5 L) and 5% dibasic sodium phosphate (18.5 L) were charged. The organic phase was then washed with saturated brine (18.5 L), dried over magnesium sulfate, filtered and evaporated to afford title compound 487 (4.63 g, 100%).

1. customovernight
2. customat 4° C.
3. temperatureThe mixture was cooled to −5° C.
4. additionborane-methyl sulfide complex (4.4 mL, 44.0 mmol) was added over 2 hours via syringe pump
5. temperatureThe reaction mixture was then gradually warmed to 40° C. over 3 hours
6. waitAfter aging 1.5 hours at 40° C.
7. temperaturethe reaction mixture was cooled to 20-25° C.
8. customslowly quenched into a 2N HCl solution (27.7 L)
9. stirringThe quenched mixture was then stirred for 1 h at 40° C
10. concentrationAmmonium hydroxide concentrated (6.3 L)
11. additionwas added
12. additioni-PrOAc (18.5 L) and 5% dibasic sodium phosphate (18.5 L) were charged
13. washThe organic phase was then washed with saturated brine (18.5 L)
14. dry with materialdried over magnesium sulfate
15. filtrationfiltered
16. customevaporated

ORD record

ord-324ef82d864f400e93cf8e1dcf17ddee

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399452B2