Phosphate → (1-Benzylpiperazin-2-yl)methanol

Temperature

100 °C

N-benzylhydroxymethylpiperazine was prepared according to the reported literature procedure: A. Naylor et al, J. Med. Chem. 1993, 36, 2075-2083. To compound 379 (2.48 g, 12.00 mmol), which was dried just before use by azeotropic distillation with toluene under reduced pressure, dissolved in anhydrous DMF (24 mL) under an argon atmosphere was successively added N,N-diisopropylethylamine (3.15 mL, 17.95 mmol), 4 Å molecular sieves and dichloropyridazinone 378 (1.68 g, 5.98 mmol). The reaction mixture was heated at 100° C. for 23 h. Upon cooling to room temperature, the mixture was poured into an aqueous pH 7 phosphate buffer solution (400 mL) and diluted with ethyl acetate (300 mL). After decantation, the aqueous solution was extracted with ethyl acetate (3×350 mL). The combined organic extract was successively washed with water (400 mL) then brine (400 mL), dried (MgSO4), filtered, and concentrated. The crude oil was recrystallized from boiling ethyl acetate (250 mL), filtered and rinsed with cold methylene chloride (70 mL) to give 1.08 g of the product 380 (41% yield) as an off-white solid. MS (M+1): m/e 447.

1. temperatureUpon cooling to room temperature
2. extractionAfter decantation, the aqueous solution was extracted with ethyl acetate (3×350 mL)
3. extractionThe combined organic extract
4. washwas successively washed with water (400 mL)
5. dry with materialbrine (400 mL), dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude oil was recrystallized
9. filtrationfiltered
10. washrinsed with cold methylene chloride (70 mL)

ORD record

ord-bde7067e771f446c8d92214d172288f9

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08232274B2