Methyl iodide → 3-Iodo-1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole

Temperature

0 °C

To a solution of 3-iodo-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (305 mg, 1.3 mmol) in THF (8.51 mL) at 0° C. was added KOtBu 1M in THF (1.82 mL, 1.82 mmol) and the mixture stirred at 0° C. for 30 min where it became a pale yellow solution then added MeI (259 mg, 114 μL, 1.82 mmol). The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane (3×30 mL), organics dried over MgSO4 and concentrated to a clear oil. Then dissolved in toluene and purified by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min) to afford the more polar desired 3-iodo-1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (177 mg, 714 μmol, 55%) as a white solid. MS (M+H)+=249; 1H NMR (CDCl3) δ: 3.78 (s, 30H), 2.68-2.79 (m, 20H), 2.51-2.58 (m, 4H). The regisomeric product, 3-iodo-2-methyl-2,4,5,6-tetrahydrocyclopenta[c]pyrazole, (125 mg, 504 μmol, 39%) was also obtained as a white solid.

1. stirringThe reaction mixture was stirred at 0° C. for 30 min
2. temperaturethen warmed to 25° C.
3. stirringstirred for 1.5 h
4. customThe reaction mixture was quenched with saturated ammonium chloride in water
5. extractionextracted with dichloromethane (3×30 mL)
6. dry with materialorganics dried over MgSO4
7. concentrationconcentrated to a clear oil
8. dissolutionThen dissolved in toluene
9. custompurified by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min)

ORD record

ord-94dec408a0ea4693a601b3359057bdc4

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2