Carbon Tetrachloride → 5-amino-1-(2-chloroethyl)-1H-pyrazole-4-carbonitrile

A suspension of 5-amino-4-cyano-1-(2hydroxyethyl)pyrazole (40 g.) and triphenylphosphine (82.7 g.) in dichloromethane (300 ml.) was cooled in a room temperature water bath while carbon tetrachloride (127 ml.) was added dropwise over 45 minutes. The resulting suspension was stirred at room temperature under nitrogen overnight, and the volatiles were then removed on a rotary evaporator, leaving an orange semisolid. This was treated with boiling EtOAc (500 ml.), chilled at 0° , filtered, and the filtrate evaporated to dryness. The residue was redissolved in THF (300 ml.) and evaporated onto flash silica gel (160 g.). This material was placed atop a column of flash silica gel (300 g.) and the desired product eluted with EtOAc/hexane (1:1 v/v). Contaminating triphenylphosphine oxide was removed by trituration with dichloromethane/hexane (1:1 v/v). The remaining solid was then recrystallized from EtOAc to give 5-amino-1-(2-chloroethyl)-4-cyanopyrazole (29.07 g.) as white crystals: m.p. 155.5-156.5 °.

1. additionwas added dropwise over 45 minutes
2. customthe volatiles were then removed on a rotary evaporator
3. customleaving an orange semisolid
4. temperaturechilled at 0°
5. filtrationfiltered
6. customthe filtrate evaporated to dryness
7. dissolutionThe residue was redissolved in THF (300 ml.)
8. customevaporated onto flash silica gel (160 g.)
9. washthe desired product eluted with EtOAc/hexane (1:1 v/v)
10. customContaminating triphenylphosphine oxide was removed by trituration with dichloromethane/hexane (1:1 v/v)
11. customThe remaining solid was then recrystallized from EtOAc

ORD record

ord-7bb7c253836a4e14ae9c8006e73f1d2f

Source dataset

uspto-grants-1987_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04705793