Acetyl chloride → 3-(1-{2-[5-(Acetylamino)-2-methylphenyl]ethyl}piperidin-4-yl)-5-fluoro-1h-indole

Temperature

0 °C

Polymer bound 3-[1-(2-{5-amino-2-methylphenyl}ethyl)piperidin-4-yl]-5-fluoro-1H-indole (100 mg, 100 μmol), triethylamine (90 μL), and dimethylaminopyridine (0.50 mL of an 0.2 M solution in dry acetonitrile) were mixed in a reactor tube. The mixture was cooled to 0° C. and treated with acetyl chloride (0.50 mL of an 1M solution in dry acetonitrile). The reaction mixture was left at 0° C. for 2 h. The resin was filtered off and washed with dry acetonitrile (3×1 mL). The resin was treated for 1 h with 1 mL of a mixture of sodium methoxide (2 mL, 5 N sodium methoxide in methanol), methanol (50 mL) and tetrahydrofuran (50 mL). After filtration, the resin was washed with methanol (1 mL). The combined filtrates were loaded on a pre-conditioned ion exchange column (500 mg SCX column, commercially available from Analytical Instruments, part no. 1210-2040), washed with acetonitrile (1 mL) and methanol (1 mL). The product was eluted with 4 M ammonia in methanol. Evaporation of volatile solvents afforded the title compound as a yellow oil (6 mg, 15 μmol). LC/MS (m/z) 394 (MH+), RT=1.98, purity: 88%.

1. filtrationThe resin was filtered off
2. washwashed with dry acetonitrile (3×1 mL)
3. additionThe resin was treated for 1 h with 1 mL of a mixture of sodium methoxide (2 mL, 5 N sodium methoxide in methanol), methanol (50 mL) and tetrahydrofuran (50 mL)
4. filtrationAfter filtration
5. washthe resin was washed with methanol (1 mL)
6. wash1210-2040), washed with acetonitrile (1 mL) and methanol (1 mL)
7. washThe product was eluted with 4 M ammonia in methanol
8. customEvaporation of volatile solvents

ORD record

ord-fddc8d8287474a30a91a14830c2ce7b1

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743809B2