p-Toluenesulfonic acid → ethyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylate

HRID 526738Notes

Reaction equation

HRID 526738 reaction equation
[I:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[I:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:4]([CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][O:12]2)[N:3]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 178469927HCID 178469927, compound

Product 1

HCID 58486565ethyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylateYield 91.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 3-iodo-1H-pyrazole-4-carboxylate (10.8 g, 40.60 mmol, 1.00 equiv), 3,4-dihydro-2H-pyran (10 g, 118.88 mmol, 2.93 equiv) and TsOH (780 mg, 4.53 mmol, 0.11 equiv) in THF (100 mL) was stirred for 2 h at 60° C. The reaction mixture was cooled to room temperature and quenched by the addition of 100 mL of saturated sodium bicarbonate solution. The resulting solution was extracted with 2×80 mL of dichloromethane. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1:20) to give 13 g (91%) of ethyl 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carboxylate as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 8.04 (s, 1H), 5.40-5.38 (m, 1H), 4.34-4.29 (m, 2H), 4.08-4.05 (m, 1H), 3.73-3.70 (m, 1H), 2.07-1.98 (m, 3H), 1.69-1.62 (m, 3H), 1.39-1.32 (m, 3H) ppm. LCMS (method C, ESI): RT=1.53 min, m/z=351.0 [M+H]+.

Workup

  1. customquenched by the addition of 100 mL of saturated sodium bicarbonate solution
  2. extractionThe resulting solution was extracted with 2×80 mL of dichloromethane
  3. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified on a silica gel column
  6. washeluted with ethyl acetate/petroleum ether (1:20)

Sources & evidence

ORD record
ord-1c25208fbdcb45929817b286789e97fe
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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