2,2-bis(4-chlorophenyl)acetamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-bis-(4-chloro-phenyl)-acetamide (0.50 g, 1.8 mmol) in THF (10 mL) at rt was added BH3-THF (1.0 M in THF, 4.5 mL, 4.5 mmol). The solution was heated at reflux for 2 h. The mixture was cooled in an ice bath, and the excess BH3 was quenched by careful addition of 10 mL of MeOH. HCl (2.0 M in MeOH, 5 mL) was added, and the resulting mixture was heated at reflux for 1 h. After cooling, the mixture was concentrated, and the residue was partitioned between 1 N HCl and Et2O. The acidic aqueous layer was basified with 10 N NaOH and extracted with Et2O (3×). The combined organic extracts were dried (MgSO4) and concentrated to provide the desired amine (181 mg, 38%). The amine was used without further purification. 1H NMR (400 MHz, CDCl3): 7.30-7.26 (m, 4H), 7.18-7.12 (m, 4H), 3.94 (t, J=7.5, 1H), 3.28 (d, J=7.6, 2H), 1.06 (br s, 2H). The solution was heated at reflux for 2 h The mixture was cooled in an ice bath the excess BH3 was quenched by careful addition of 10 mL of MeOH HCl (2.0 M in MeOH, 5 mL) was added the resulting mixture was heated at reflux for 1 h After cooling the mixture was concentrated the residue was partitioned between 1 N HCl and Et2O extracted with Et2O (3×) The combined organic extracts were dried (MgSO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2,2-bis-(4-chloro-phenyl)-acetic acid (0.50 g, 1.8 mmol) in SOCl2 (5 mL) was heated at reflux for 1 h. The mixture was concentrated, and the residue was azeotroped with toluene (3×). The crude acid chloride was stirred in DCM (10 mL) at rt and treated with NH3 (0.5 M in dioxane, 14 mL, 7.5 mmol). After 1 h, the reaction mixture was concentrated, and the residue was diluted with satd. aq. NaHCO3 and extracted with DCM (3×). The combined organics were dried (Na2SO4) and concentrated to provide the amide as a white solid (0.50 g, 100%). The amide was used without further purification. 1H NMR (400 MHz, CDCl3): 7.35-7.28 (m, 4H), 7.23-7.17 (m, 4H), 5.69 (br s, 1H), 5.53 (br s, 1H), 4.87 (s, 1H). was heated at reflux for 1 h The mixture was concentrated the residue was azeotroped with toluene (3×) the reaction mixture was concentrated the residue was diluted with satd aq. NaHCO3 and extracted with DCM (3×) The combined organics were dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2,2-bis-(4-chloro-phenyl)-acetic acid (0.50 g, 1.8 mmol) in SOCl2 (5 mL) was heated at reflux for 1 h. The mixture was concentrated, and the residue was azeotroped with toluene (3×). The crude acid chloride was stirred in DCM (10 mL) at rt and treated with NH3 (0.5 M in dioxane, 14 mL, 7.5 mmol). After 1 h, the reaction mixture was concentrated, and the residue was diluted with satd. aq. NaHCO3 and extracted with DCM (3×). The combined organics were dried (Na2SO4) and concentrated to provide the amide as a white solid (0.50 g, 100%). The amide was used without further purification. 1H NMR (400 MHz, CDCl3): 7.35-7.28 (m, 4H), 7.23-7.17 (m, 4H), 5.69 (br s, 1H), 5.53 (br s, 1H), 4.87 (s, 1H). was heated at reflux for 1 h The mixture was concentrated the residue was azeotroped with toluene (3×) the reaction mixture was concentrated the residue was diluted with satd aq. NaHCO3 and extracted with DCM (3×) The combined organics were dried (Na2SO4) concentrated