(E)-3-chloro-2-fluorobenzaldehyde oxime synthesis

Yield:890934-28-8 53.2%

Reaction Conditions:

with hydroxylamine hydrochloride;triethylamine in tetrahydrofuran at 20;

Steps:

25.1 Example 25:4-((S)-2-((R)-3-(3-chloro-2-fluorophenyl)-4,5-dihydroisoxazole-5-carbonyl)-5-(4-methyl) 2-oxopiperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamido)benzoic acid intermediatePreparation of 1-(3,4-dihydroisoquinolin-5-yl)-4-methylpiperidin-2-one Preparation of intermediate 3-(3-chloro-2-fluorobenzene)-4,5-dihydroisoxazole-5-carboxylic acid first step:Preparation of 3-chloro-2-fluorobenzaldehyde oxime compound

3-Chloro-2-fluorobenzaldehyde (50.0 g, 0.32 mol) and hydroxylamine hydrochloride (22.2 g, 0.32 mol)Dissolved in THF (400 mL), added Et3N (32.3 g, 0.32 mol) and stirred overnight.The reaction solution was quenched with water, extracted with ethyl acetate, and the organic phase was washed twice with saturated aqueous NaCl solution.Dry over anhydrous magnesium sulfate, filter, and concentrate the concentrated crude product on a silica gel column to give the desired 3-chloro-2-fluorobenzaldehyde oxime as a white solid.(29.1g, 53.2%)

References:

CN107540659,2018,A Location in patent:Paragraph 0182-0183; 0296; 0303