Potassium tert-butoxide → HCID 68426422、化合物

温度

-78 °C

A mixture of 4-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester (302 mg, 0.58 mol) in THF (5 mL) was added drop wise a solution of 1 M KOtBu in THF (702 μL, 0.70 mmol) at −78° C. The mixture was stirred at −78° C. for 15 min, warmed to room temperature and stirred at that temperature for 1.5 h before it was quenched with brine, extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to a yellow foam (469 mg). It was dissolved in dichloromethane (10 mL) and TFA (2.5 mL) was added. The mixture was stirred at room temperature for 1 h before it was concentrated in vacuo. It was redissolved in dichloromethane, triethylamine (923 μL) was added. The mixture was stirred under air overnight before it was partitioned between dichloromethane and water, the organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and dichloromethane to give the title compound as a white solid (257 mg): MS: (+) m/z 330.0 (M+1).

1. temperaturewarmed to room temperature
2. stirringstirred at that temperature for 1.5 h before it
3. customwas quenched with brine
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo to a yellow foam (469 mg)
8. dissolutionIt was dissolved in dichloromethane (10 mL)
9. additionTFA (2.5 mL) was added
10. stirringThe mixture was stirred at room temperature for 1 h before it
11. concentrationwas concentrated in vacuo
12. dissolutionIt was redissolved in dichloromethane
13. additiontriethylamine (923 μL) was added
14. stirringThe mixture was stirred under air overnight before it
15. customwas partitioned between dichloromethane and water
16. washthe organic layer was washed with brine
17. dry with materialdried over anhydrous sodium sulfate
18. concentrationconcentrated in vacuo
19. customThe residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and dichloromethane

ORDレコード

ord-b15059aad254442bb9d0e7ba1480cbf3

出典データセット

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07696223B2