N-tert-butyl-2-iodoacetamide

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:

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: 3-[Tert.-butoxycarbonylamino]-8-methyl-2-oxo-5-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine (1.4 g, 3.8 mmol), N-t-butyl iodoacetamide (1.1 g, 4.56 mmol) and tetrabutylammonium bromide (85 mg, 0.26 mmol) were dissolved in dry tetrahydrofuran (25 ml) under nitrogen. Powder potassium hydroxide (0.3 g, 4.5 mmol) was added in one portion and the reaction was stirred for 5 hours. The reaction was diluted with ethyl acetate (25 ml) and washed with water (2×50 ml) and brine. After drying over magnesium sulfate, the solvent was evaporated in vacuo to provide the desired product as a foam; 2 g, >100% yield. This contained some excess iodoacetamide, but was suitable for use in the next reaction. IR (KBr) 1720, 1680, 1659, 1614 cm-1. 1H NMR (CDCl3) δ 7.28-7.07 (m, 6), 7.00 (d, 2), 6.05 (s, 1), 5.49 (d, 1), 4.34 (m, 1), 4.08 (d, 1), 3.62 (d, 1), 2.95 (dt, 1), 2.63 (t, 1), 2.60 (d, 1), 2.33 (s, 3), 1.41 (s, 9), 1.32 (s, 9). washed with water (2×50 ml) and brine After drying over magnesium sulfate the solvent was evaporated in vacuo

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

Procedure: Following the previous expermental procedure, 3-[3-(3-chloro-phenyl)-ureido]-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-benzo[b]azepine (0.4 g, 1 mmol) was alkylated with N-tert.-butyl iodoacetamide (0.28 g, 1.2 mmol) to provide the title compound as a white solid, 0.3 g, 59% yield. mp 222-5° C. 1H NMR (CDCl3) δ 8.03 (s, 1), 7.59 (t, 1), 7.34-7.15 (m, 3), 7.10 (d, 1),7.01 (t, 1), 6.91 (d, 1), 6.83 (d, 1), 6.43 (bd, 1), 6.43 (bd, 1), 6.31 (s, 1), 4.95 (d, 1), 4.54 (m, 1), 3.59 (d, 1), 2.66 (m, 1), 2.53 (t, 1), 2.18 (bd, 1), 1.78 (m, 1), 1.59 (m, 1), 1.4 (s, 9), 1.29-0.78 (m, 6), 0.58 (m, 1).