ChemicalBook CAS DataBase List 2-CHLOROANILINE HYDROCHLORIDE

2-CHLOROANILINE HYDROCHLORIDE synthesis

4synthesis methods

Product Name:2-CHLOROANILINE HYDROCHLORIDE
CAS Number:137-04-2
Molecular formula:C6H7Cl2N
Molecular Weight:164.03

533-17-5
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$7.00/5g

925-90-6 Synthesis

925-90-6
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$12.00/5ml

137-04-2
74 suppliers
$14.14/1gm:

Yield: 78%

Reaction Conditions:

Stage #1:N-(2-chlorophenyl)acetamide with 2-fluoropyridine;trifluoromethylsulfonic anhydride in dichloromethane at 0; for 0.5 h;
Stage #2:ethylmagnesium bromide with cerium(III) chloride in tetrahydrofuran;dichloromethane at -78; for 2 h;
Stage #3: with hydrogenchloride in ethyl acetate

Steps:

General procedure for N-deacylation of secondary amides
General procedure: Tf₂O (185μL, 1.1mmol) was added dropwise to a cooled (0°C) solution of amide (1.0mmol) and 2-fluoropyridine (103μL, 1.2mmol) in dichloromethane (4mL). After stirring at 0°C for 30min, the mixture was cannulated to a freshly prepared organocerium reagent/complex (3.0mmol) in THF (15mL) at -78°C and stirred for 2h. Aqueous HCl solution (3mol/L, 5mL) was added to quench the reaction and the mixture was allowed to warm to r.t. and stirred for 2h. Ammonium hydroxide solution (25%, 5mL) was then added to the mixture. The organic layer was separated and the aqueous phase was extracted with diethyl ether (3× 10mL). The combined organic layers were washed with brine (3× 3mL) and concentrated under reduced pressure to about 1/3 volume. The residual organic phase was then extracted with aqueous HCl solution (3mol/L, 3× 5mL). The separated organic phase was washed with brine (5mL), dried over anhydrous MgSO₄, filtered, and concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel to afford ketone. The aqueous phases were combined, washed with diethyl ether (5mL), basified with an ammonium hydroxide solution (25%, 5mL) and back-extracted with diethyl ether (5× 20mL). The ether layers were combined, washed with brine (5mL), dried over anhydrous MgSO₄, filtered, acidified with a solution of HCl in ethyl acetate (3mol/L, 5mL) and concentrated under reduced pressure to afford the desired amine hydrochloride salt.

References:

Wang, Ai-E.;Chang, Zong;Liu, Yong-Peng;Huang, Pei-Qiang [Chinese Chemical Letters,2015,vol. 26,# 9,p. 1055 - 1058] Location in patent:supporting information