Water → Methyl 4-(2-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate

Iodomethane (0.029 mL, 0.46 mmol) was added to methyl 4-(2-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl)acetyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (57) (0.100 g, 0.23 mmol) and potassium carbonate (0.048 g, 0.35 mmol) in DMF (5 mL). The resulting suspension was stirred at room temperature for 16 hours. The reaction was incomplete and further iodomethane (0.029 mL, 0.46 mmol) was added and the suspension was stirred at room temperature for a further 4 hours. The reaction was incomplete so the temperature was increased to 50° C. and the reaction mixture was stirred for a further 3 hours. The reaction mixture was poured into water (75 mL), extracted with EtOAc (3×50 mL), the combined organic layers were washed with water (50 mL) and saturated brine (50 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the desired material as a colourless gum (0.082 g, 79% yield); m/z (LC-MS, ESI+), RT=2.06 min (M+H=445.30).

1. stirringthe suspension was stirred at room temperature for a further 4 hours
2. temperaturewas increased to 50° C.
3. stirringthe reaction mixture was stirred for a further 3 hours
4. extractionextracted with EtOAc (3×50 mL)
5. washthe combined organic layers were washed with water (50 mL) and saturated brine (50 mL)
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. customevaporated
9. customto afford crude product
10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% ethyl acetate in isohexane
11. customPure fractions were evaporated to dryness

ORDレコード

ord-eb2840e287664ddbb56d98efc178fe70

出典データセット

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08129380B2