Water → 4-iodo-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole

Temperature

0 °C

As shown in step 2-ii of Scheme 2, sodium hydride (6.101 mL of 60% NaH/mineral oil, 137.3 mmol) was added slowly to a solution of 4-iodopyrazole (24.21 g, 124.8 mmol) in 200 mL of anhydrous DMF at 0° C. The solution was stirred for 1 hour at 0° C. and tetrahydro-2H-pyran-4-yl methanesulfonate (Compound 1010, 22.5 g, 124.8 mmol) in 100 mL of anhydrous DMF was added dropwise. The reaction mixture was heated at 100° C. for 18 hours, at which time an additional 8.0 g of (Compound 1010) in 25 mL of anhydrous DMF was added dropwise. The reaction mixture was heated at 100° C. for an additional 24 hours. The mixture was cooled to room temperature and 100 mL of water was added. The mixture was extracted with EtOAc (3×100 mL) and the combined organics were washed with water, washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford a semi-solid. Recrystallization from DCM yielded 1-(tetrahydro-2H-pyran-4-yl)-4-iodo-1H-pyrazole (Compound 1011, 11.96 g). A second crop of crystals was obtained upon trituration of the mother liquor with hexanes (5.26 g, 49.6% total yield): ESMS (M+H)=279.0.

1. additionwas added dropwise
2. temperatureThe reaction mixture was heated at 100° C. for an additional 24 hours
3. temperatureThe mixture was cooled to room temperature
4. extractionThe mixture was extracted with EtOAc (3×100 mL)
5. washthe combined organics were washed with water
6. washwashed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto afford a semi-solid
11. customRecrystallization from DCM

ORD record

ord-dc7b716063b4471d9ffc0628c2a6f440

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518938B2