反応 #535755

反応方程式

9a

4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

→

9b

4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

溶媒

—

solution

HCl

dioxane

反応条件

後処理

1. 1
   その他the solvent was removed
2. 2
   温度40 mL of toluene and cooled to 0° C
3. 3
   workup.ADDITIONIsopropyl chloroformate (60 mL of a 1 M solution in toluene, 1.2 eq) and diisopropylethylamine (24 mL) were added
4. 4
   workup.STIRRINGThe mixture was stirred for 36 h
5. 5
   洗浄washed with 1 M HCl (3×100 mL), 100 mL of water and 100 mL of brine
6. 6
   その他The solvent was evaporated
7. 7
   温度cooled at 0° C.
8. 8
   workup.STIRRINGstirred for 2 h
9. 9
   その他to give a precipitate which
10. 10
    ろ過was filtered
11. 11
    洗浄washed with hexane

実験手順

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%).

出典