Hydrochloric Acid → (4-Amino-2,6-dichloro-phenyl)-acetonitrile

Temperature

75 °C

A solution of cyano-(2,6-dichloro-4-nitro-phenyl)-acetic acid tert-butyl ester (43) (78.69 g, crude) in ethanol (320 mL) at 25° C. was treated with concentrated hydrochloric acid (160 mL). The reaction was fitted with a reflux condenser and then was heated to 75° C. At this time, the resulting homogeneous solution was treated portion wise with tin(II) chloride dihydrate (225.64 g, 1.0 mol). Upon complete addition of the tin(II) chloride dihydrate, the reaction was warmed to 110-115° C. where it was stirred for 3 h. At this time, the reaction was cooled to 25° C. and then was diluted with ethyl acetate (1.5 L). The resulting solution was carefully neutralized with a saturated aqueous sodium carbonate solution (1.0 L). The resulting thick mixture was filtered through filter paper via vacuum filtration and was washed with ethyl acetate until no material was detected in the filtrate. The filtrate was then transferred to a separatory funnel where the resulting layers were separated. The organics were washed consecutively with a 1N aqueous hydrochloric acid solution (1×250 mL), a saturated aqueous sodium carbonate solution (1×250 mL), a 1N aqueous hydrochloric acid solution (1×250 mL), and a saturated aqueous sodium chloride solution (1×250 mL). The organics were then dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded (4-amino-2,6-dichloro-phenyl)-acetonitrile (44) (25.95 g, 58%) as a yellow solid; EL-HRMS m/e calcd for C8H6Cl2N2 (M+) 199.9908, found 199.9906. Exact Mass=199.9908; Molecular Weight=201.06.

1. customThe reaction was fitted with a reflux condenser
2. temperaturethe reaction was warmed to 110-115° C. where it
3. temperatureAt this time, the reaction was cooled to 25° C.
4. filtrationThe resulting thick mixture was filtered
5. filtrationthrough filter paper
6. filtrationvia vacuum filtration
7. washwas washed with ethyl acetate until no material
8. customThe filtrate was then transferred to a separatory funnel
9. customwhere the resulting layers were separated
10. washThe organics were washed consecutively with a 1N aqueous hydrochloric acid solution (1×250 mL)
11. dry with materialThe organics were then dried with magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated under vacuum

ORD record

ord-6d394f5cbe3941aa92b4a1914304a932

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

USRE046024E1