N-(2-methoxyphenyl)-2,2-dimethylpropanamide

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

Procedure: n-Butyllithium (1.6M solution in hexane; 200 ml, 0.32 mol) was added dropwise under nitrogen at −10° C. to a stirred solution of N-(2-methoxyphenyl)pivalamide (27.6 g, 0.133 mol) in tetrahydrofuran (600 ml), the mixture was allowed to warm to ambient temperature, stirred for a further 2 hours, then it was added to a large excess of crushed solid carbon dioxide. The mixture was allowed to warm to ambient temperature, 3M hydrochloric acid (200 ml) was added and the tetrahydrofuran was removed in vacuo. The resulting solid was collected by filtration and crystallised from acetonitrile to give 3-methoxy-2-pivalamidobenzoic acid (21 g; 63%) as a solid, m.pt. 117–120° C. Concentration of the liquor yielded a second crop (2.6 g; 8%). to warm to ambient temperature the tetrahydrofuran was removed in vacuo The resulting solid was collected by filtration crystallised from acetonitrile

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

Procedure: Pivaloyl chloride (120 g, 1 mol) was added dropwise at ambient temperature to a stirred solution of 2-methoxyaniline (123 g, 1 mol) and triethylamine (111 g, 1.1 mol) in 1,4-dioxane (1200 ml), the mixture was stirred at ambient temperature for 2 hours, then it was poured into water (3000 ml). The product was extracted into ethyl acetate (3×300 ml), then the combined extracts were dried (MgSO4) and the solvents were removed in vacuo to give N-(2-methoxyphenyl)pivalamide (198 g; 96%) as a low-melting solid which was used without further purification. The product was extracted into ethyl acetate (3×300 ml) the combined extracts were dried (MgSO4) the solvents were removed in vacuo

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

Procedure: n-Butyllithium (1.6M solution in hexane; 200 ml, 0.32 mol) was added dropwise under nitrogen at −10° C. to a stirred solution of N-(2-methoxyphenyl)pivalamide (27.6 g, 0.133 mol) in tetrahydrofuran (600 ml), the mixture was allowed to warm to ambient temperature, stirred for a further 2 hours, then it was added to a large excess of crushed solid carbon dioxide. The mixture was allowed to warm to ambient temperature, 3M hydrochloric acid (200 ml) was added and the tetrahydrofuran was removed in vacuo. The resulting solid was collected by filtration and crystallised from acetonitrile to give 3-methoxy-2-pivalamidobenzoic acid (21 g; 63%) as a solid, m.pt. 117-120° C. Concentration of the liquor yielded a second crop (2.6 g; 8%). to warm to ambient temperature the tetrahydrofuran was removed in vacuo The resulting solid was collected by filtration crystallised from acetonitrile

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

Procedure: n-Butyllithium (1.6M solution in hexane; 200 ml, 0.32 mol) was added dropwise under nitrogen at −10° C. to a stirred solution of N-(2-methoxyphenyl)pivalamide (27.6 g, 0.133 mol) in tetrahydrofuran (600 ml), the mixture was allowed to warm to ambient temperature, stirred for a further 2 hours, then it was added to a large excess of crushed solid carbon dioxide. The mixture was allowed to warm to ambient temperature, 3M hydrochloric acid (200 ml) was added and the tetrahydrofuran was removed in vacuo. The resulting solid was collected by filtration and crystallised from acetonitrile to give 3-methoxy-2-pivalamidobenzoic acid (21 g; 63%) as a solid, m.pt. 117-120° C. Concentration of the liquor yielded a second crop (2.6 g; 8%). to warm to ambient temperature the tetrahydrofuran was removed in vacuo The resulting solid was collected by filtration crystallised from acetonitrile

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

Procedure: Pivaloyl chloride (120 g, 1 mol) was added dropwise at ambient temperature to a stirred solution of 2-methoxyaniline (123 g, 1 mol) and triethylamine (111 g, 1.1 mol) in 1,4-dioxane (1200 ml), the mixture was stirred at ambient temperature for 2 hours, then it was poured into water (3000 ml). The product was extracted into ethyl acetate (3×300 ml), then the combined extracts were dried (MgSO4) and the solvents were removed in vacuo to give N-(2-methoxyphenyl)pivalamide (198 g; 96%) as a low-melting solid which was used without further purification. The product was extracted into ethyl acetate (3×300 ml) the combined extracts were dried (MgSO4) the solvents were removed in vacuo

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

Procedure: Pivaloyl chloride (120 g, 1 mol) was added dropwise at ambient temperature to a stirred solution of 2-methoxyaniline (123 g, 1 mol) and triethylamine (111 g, 1.1 mol) in 1,4-dioxane (1200 ml), the mixture was stirred at ambient temperature for 2 hours, then it was poured into water (3000 ml). The product was extracted into ethyl acetate (3×300 ml), then the combined extracts were dried (MgSO4) and the solvents were removed in vacuo to give N-(2-methoxyphenyl)pivalamide (198 g; 96%) as a low-melting solid which was used without further purification. The product was extracted into ethyl acetate (3×300 ml) the combined extracts were dried (MgSO4) the solvents were removed in vacuo

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

Procedure: n-Butyllithium (1.6M solution in hexane; 200 ml, 0.32 mol) was added dropwise under nitrogen at −10° C. to a stirred solution of N-(2-methoxyphenyl)pivalamide (27.6 g, 0.133 mol) in tetrahydrofuran (600 ml), the mixture was allowed to warm to ambient temperature, stirred for a further 2 hours, then it was added to a large excess of crushed solid carbon dioxide. The mixture was allowed to warm to ambient temperature, 3M hydrochloric acid (200 ml) was added and the tetrahydrofuran was removed in vacuo. The resulting solid was collected by filtration and crystallised from acetonitrile to give 3-methoxy-2-pivalamidobenzoic acid (21 g; 63%) as a solid, m.pt. 117–120° C. Concentration of the liquor yielded a second crop (2.6 g; 8%). to warm to ambient temperature the tetrahydrofuran was removed in vacuo The resulting solid was collected by filtration crystallised from acetonitrile

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

Procedure: Pivaloyl chloride (120 g, 1 mol) was added dropwise at ambient temperature to a stirred solution of 2-methoxyaniline (123 g, 1 mol) and triethylamine (111 g, 1.1 mol) in 1,4-dioxane (1200 ml), the mixture was stirred at ambient temperature for 2 hours, then it was poured into water (3000 ml). The product was extracted into ethyl acetate (3×300 ml), then the combined extracts were dried (MgSO4) and the solvents were removed in vacuo to give N-(2-methoxyphenyl)pivalamide (198 g; 96%) as a low-melting solid which was used without further purification. The product was extracted into ethyl acetate (3×300 ml) the combined extracts were dried (MgSO4) the solvents were removed in vacuo