Tert-butyl 4-[(6-chloro-5-methylpyrimidin-4-yl)oxy]piperidine-1-carboxylate → 4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

9a was dissolved in a 4 M solution of HCl in dioxane (60 mL). The solution was stirred at room temperature for 3 h and the solvent was removed. The residue was taken up in 200 mL of DCM and 40 mL of toluene and cooled to 0° C. Isopropyl chloroformate (60 mL of a 1 M solution in toluene, 1.2 eq) and diisopropylethylamine (24 mL) were added. The mixture was stirred for 36 h, washed with 1 M HCl (3×100 mL), 100 mL of water and 100 mL of brine. The solvent was evaporated and the residue taken up in 50 mL of hexane, cooled at 0° C. and stirred for 2 h to give a precipitate which was filtered and washed with hexane. 2.89 g of 9b were obtained. The filtrate was concentrated and recrystallized with IPA. Some light yellow crystals were obtained, filtered and washed with IPA to give 3.38 g of 9b. The filtrate was concentrated and purified on silica gel (eluent: 20% ethyl acetate in hexane) to give 2.2 g of 9b. Total yield of 9b: 8.47 g (54%).

1. customthe solvent was removed
2. temperature40 mL of toluene and cooled to 0° C
3. additionIsopropyl chloroformate (60 mL of a 1 M solution in toluene, 1.2 eq) and diisopropylethylamine (24 mL) were added
4. stirringThe mixture was stirred for 36 h
5. washwashed with 1 M HCl (3×100 mL), 100 mL of water and 100 mL of brine
6. customThe solvent was evaporated
7. temperaturecooled at 0° C.
8. stirringstirred for 2 h
9. customto give a precipitate which
10. filtrationwas filtered
11. washwashed with hexane

ORD-Eintrag

ord-eff6a95bd1824e58b8cf1ce49b43bbe9

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08481731B2