Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate → [4-(4-Methylpiperazin-1-yl)phenyl]methanol

A solution of 4-(4-formyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.3 g, 4.47 mmol) in THF (50 mL) was mixed with LAH (0.7 g, 17.87 mmol) and stirred at reflux for 14 h. The reaction was quenched at room temperature by adding KOH aqueous (14 N, 20 mL). The supernatant was decanted and combined with DCM washings, then diluted with water (50 mL). The mixture was extracted with DCM (3×50 mL) followed by concentration using a rotary evaporator to give [4-(4-methyl-piperazin-1-yl)-phenyl]-methanol (0.82 g, 89%). To a solution of DMSO (0.56 mL, 7.96 mmol) in DCM (50 mL) at −78° C. was added oxalyl chloride (0.7 mL, 7.96 mmol) and the resulting mixture was stirred at −78° C. for 0.5 h. A solution of [4-(4-methyl-piperazin-1-yl)-phenyl]-methanol (0.82 g, 3.98 mmol) in DCM (20 mL) was slowly added. The reaction was stirred at −78° C. for 1.5 h. Triethylamine (1.7 mL, 11.94 mmol) was added and the reaction was allowed to gradually warm up to room temperature. After stirring for 4 h the reaction was quenched by adding sodium bicarbonate aqueous (1 N, 50 mL). The mixture was extracted with DCM (3×50 mL) followed by concentration to afford a residue, which was further purified by column chromatography to yield 4-(4-methyl-piperazin-1-yl)-benzaldehyde (0.5 g, 61%).

1. temperatureat reflux for 14 h
2. customThe reaction was quenched at room temperature
3. additionby adding KOH aqueous (14 N, 20 mL)
4. customThe supernatant was decanted
5. additiondiluted with water (50 mL)
6. extractionThe mixture was extracted with DCM (3×50 mL)
7. concentrationfollowed by concentration
8. customa rotary evaporator

ORD-Eintrag

ord-104b18a4eab9494c921bf699c96c646c

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09199990B2