Trifluoroacetic acid → (2-Chloro-3-fluorophenyl)methanamine hydrochloride

温度

0 °C

To a solution of NaBH4 (24.3 g, 0.643 mol) in THF (400 mL) was added TFA (48 mL, 0.643 mol) slowly at 0° C. After the addition was completed, the mixture was stirred at 0° C. for about 20 min. 2-Chloro-3-fluorobenzonitrile (20 g, 0.128 mol) in THF (100 mL) was then added slowly into the mixture at 0° C. The mixture was stirred from 0° C. to RT until no starting material was observed by LCMS. Half of the solvent was removed, then 10% HCl (250 mL) was added slowly into the residue at 0° C. The mixture was warmed up and heated to reflux until no boron complex was observed by LCMS. The mixture was extracted by diethyl ether. The aqueous solution was basified to pH 8-10 using NaOH (3 N), extracted with EtOAc. The organic layers were combined and concentrated to about 300 mL. HCl (4 N, 50 mL) was added slowly into the resulting solution. The white solid was precipitated and collected by filtration to give (2-chloro-3-fluorophenyl)methanamine hydrochloride (21 g, 84%). LRMS (M+H+) m/z 160.1.

1. additionAfter the addition
2. stirringThe mixture was stirred from 0° C. to RT until no starting material
3. customHalf of the solvent was removed
4. addition10% HCl (250 mL) was added slowly into the residue at 0° C
5. temperatureThe mixture was warmed up
6. temperatureheated
7. temperatureto reflux until no boron complex
8. extractionThe mixture was extracted by diethyl ether
9. extractionextracted with EtOAc
10. concentrationconcentrated to about 300 mL
11. additionHCl (4 N, 50 mL) was added slowly into the resulting solution
12. customThe white solid was precipitated
13. filtrationcollected by filtration

ORDレコード

ord-dff726fadba34febbbef67d741d6a5b7

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08088793B2