2-cyano-N-cyclohexylacetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Cyanoacetic acid (4.26 g, 50 mmol) and cyclohexylamine (4.96 g, 50 mmol) were dissolved in DCM (100 mL). EDCI (10.51 g, 55 mmol) was added and the mixture stirred at ambient temperature for 24 h. The reaction mixture was washed with water (2×100 mL), dried (MgSO4) and evaporated to leave a yellow solid residue which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-100%) to provide the title compound as a white solid (5.66 g, 68%). The reaction mixture was washed with water (2×100 mL) dried (MgSO4) evaporated to leave a yellow solid residue which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-100%)

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

Procedure: 2-cyano-N-cyclohexyl-acetamide (Intermediate #18) (1.35 g, 8.09 mmol) was suspended in acetic anhydride (20 mL). Triethyl orthoformate (3.91 g, 21 mmol) was added and the mixture heated to reflux for 5 h. The reaction mixture was cooled to ambient and to volatiles removed by evaporation in vacuo to leave a brown oil which was which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-10%) to give the title compound as a solid (637 mg, 35%) the mixture heated to reflux for 5 h The reaction mixture was cooled to ambient and to volatiles removed by evaporation in vacuo to leave a brown oil which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-10%)

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

Procedure: Cyanoacetic acid (4.26 g, 50 mmol) and cyclohexylamine (4.96 g, 50 mmol) were dissolved in DCM (100 mL). EDCI (10.51 g, 55 mmol) was added and the mixture stiffed at ambient temperature for 24 h. The reaction mixture was washed with water (2×100 mL), dried (MgSO4) and evaporated to leave a yellow solid residue which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-100%) to provide the title compound as a white solid (5.66 g, 68%). The reaction mixture was washed with water (2×100 mL) dried (MgSO4) evaporated to leave a yellow solid residue which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-100%)

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

Procedure: 2-cyano-N-cyclohexyl-acetamide (Intermediate #18) (1.35 g, 8.09 mmol) was suspended in acetic anhydride (20 mL). Triethyl orthoformate (3.91 g, 21 mmol) was added and the mixture heated to reflux for 5 h. The reaction mixture was cooled to ambient and volatiles removed by evaporation in vacuo to leave a brown oil which was which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-10%) to give the title compound as a solid (637 mg, 35%) the mixture heated to reflux for 5 h The reaction mixture was cooled to ambient and volatiles removed by evaporation in vacuo to leave a brown oil which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-10%)