4H-Azepin-4-one, 3-broMohexahydro-5-Methyl-1-[(4-Methylphenyl)sulfonyl]- synthesis

Yield:1247885-24-0 30%

Reaction Conditions:

Stage #1: 5-methyl-1-tosylazepan-4-onewith lithium diisopropyl amide in tetrahydrofuran at -78;
Stage #2: with bromine in tetrahydrofuran at -78; for 4 h;
Stage #3: with sodium hydrogencarbonate in tetrahydrofuran;water; for 0.5 h;

Steps:

215.e

LDA (10 niL, 20 mmol) in dry THF (20 niL) was added dropwise to a solution of 5-methyl-l-tosylazepan-4-one (5.6 g, 20 mmol) in dry THF (100 mL) at -78 ⁰C. Bromine (3.2 g, 20 mmol) was added dropwise over a period of 1 h. The reaction was stirred at -78 ⁰C for 3 h. Saturated NaHCCβ was added and the resulting biphasic solution was stirred for 30 minutes. The layers were then separated and the aqueous layer was extracted with DCM. The combined organic layers were dried over sodium sulfate, filtered and evaporated to obtain the crude product. Purification by column chromatography gave the title compound as a yellow solid (2.1 g, 30%); LC/MS: m/e = 363 (M+H)⁺.

References:

WO2010/114971,2010,A1 Location in patent:Page/Page column 232