Methanol → HCID 58355670, compound

Temperature

70 °C

1-tert-Butyl 3-methyl(3R,5S)-5-[{[1-(2-fluorophenyl)-5-(hydroxymethyl)-1H-1,2,3-triazol-4-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (1.05 g) was dissolved in THF (10 ml)-methanol (8 ml)-water (8 ml), 8M aqueous sodium hydroxide solution (600 μl) was added and the mixture was stirred at 70° C. for 1.5 hr. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, neutralized with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue, morpholine, 1-hydroxybenzotriazole (150 mg) and triethylamine (700 μl) were dissolved in acetonitrile (20 ml), WSC•HCL (555 mg) was added and the mixture was stirred at room temperature for 8 hr. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate and washed with water. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (10:90-100:0) was concentrated under reduced pressure to give the object product (764 mg).

1. additionwas added
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated under reduced pressure
4. additionThe residue was diluted with water
5. extractionextracted with ethyl acetate
6. washThe extract was washed with saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe solvent was evaporated under reduced pressure
9. dissolutionThe residue, morpholine, 1-hydroxybenzotriazole (150 mg) and triethylamine (700 μl) were dissolved in acetonitrile (20 ml)
10. additionWSC•HCL (555 mg) was added
11. stirringthe mixture was stirred at room temperature for 8 hr
12. concentrationThe reaction mixture was concentrated under reduced pressure
13. additiondiluted with ethyl acetate
14. washwashed with water
15. washThe organic layer was washed with saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. customThe solvent was evaporated under reduced pressure
18. washa fraction eluted with ethyl acetate-hexane (10:90-100:0)
19. concentrationwas concentrated under reduced pressure

ORD record

ord-be00251cdc014e78bcd746da21632455

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664380B2