3-methyl-1H-3-benzazepin-2-one

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: A THF (0.5 L) solution of 3-methyl-2,3-dihydro-1H-3-benzazepin-2-one (113.8 g, 0.657 mol) was cooled to 0° C. and isoamyl nitrite (100.75 g, 0.86 mol) was added dropwise. To the resulting mixture was added LiHMDS (1 N THF solution, 854 mL, 0.854 mol) at a rate such that the temperature remained below 10° C. After addition, the reaction was allowed to stir at room temperature for 2-3 h while monitoring for the reaction progress by HPLC. Upon completion of the reaction, the mixture was cooled to 0° C., and the pH adjusted from 12 to 2-3 using aqueous HCl (2N). The resulting precipitate was stirred for 12-16 h before isolation by filtration and drying to provide 86.3 g (64.9%) of 1-hydroxyimino-3-methyl-2,3-dihydro-1H-3-benzazepin-2-one; mp=225-226° C.; (M+H)+=203.0. remained below 10° C After addition Upon completion of the reaction the mixture was cooled to 0° C. The resulting precipitate was stirred for 12-16 h before isolation by filtration drying

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

Procedure: A THF (0.5 L) solution of 3-methyl-2,3-dihydro-1H-3-benzazepin-2-one (113.8 g, 0.657 mol) was cooled to 0° C. and isoamyl nitrite (100.75 g, 0.86 mol) was added dropwise. To the resulting mixture was added LiHMDS (1 N THF solution, 854 mL, 0.854 mol) at a rate such that the temperature remained below 10° C. After addition, the reaction was allowed to stir at room temperature for 2-3 h while monitoring for the reaction progress by HPLC. Upon completion of the reaction, the mixture was cooled to 0° C., and the pH adjusted from 12 to 2-3 using aqueous HCl (2N). The resulting precipitate was stirred for 12-16 h before isolation by filtration and drying to provide 86.3 g (64.9%) of 1-hydroxyimino-3-methyl-2,3-dihydro-1H-3-benzazepin-2-one; mp=225-226° C.; (M+H)+=203.0. remained below 10° C After addition Upon completion of the reaction the mixture was cooled to 0° C. The resulting precipitate was stirred for 12-16 h before isolation by filtration drying

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 L Morton flask under a strong nitrogen atmosphere was added H2SO4, (1.42 L) and N-methyl-N-(2,2-dimethoxyethyl)phenylacetamide (712 g, 3 mol) was added dropwise to the reaction flask which caused an exotherm (22 to 78° C.). The resulting reaction was then heated to 110° C. for 3 h then cooled to room temperature and transferred to a 20 L Morton flask. At less than 10° C., the reaction mixture was quenched with aqueous sodium hydroxide (9.18 L, 5 N). Extractive workup with ethyl acetate (2×2.85 L), drying with sodium sulfate followed by concentrating to a solid, provided 520 g (73.5%) of 3-methyl-2,3-dihydro-1H-3-benzazepin-2-one as a solid. This material may be recrystallized from MTBE for added purity to give a solid, mp=81-82° C.; (M+H)+=174.2. was added dropwise to the reaction flask which an exotherm (22 to 78° C.) The resulting reaction then cooled to room temperature At less than 10° C., the reaction mixture was quenched with aqueous sodium hydroxide (9.18 L, 5 N) Extractive workup with ethyl acetate (2×2.85 L), drying with sodium sulfate by concentrating to a solid