2-Methylbenzenesulfonic acid → HCID 90461215, compound

HRID 1846248Notes

Reaction equation

HRID 1846248 reaction equation
[I:1][C:2]1[NH:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.C1(C)C(S(O)(=O)=O)=CC=CC=1.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[I:1][C:2]1[N:6]([CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)[N:5]=[C:4]([CH3:7])[C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

7

Reactant 4

HCID 69252-Methylbenzenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 178469275ethyl 3-iodo-5-methyl-1H-pyrazole-4-carboxylate

Product 1

HCID 90461215HCID 90461215, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 5-iodo-3-methyl-1H-pyrazole-4-carboxylate (2.1 g, 7.50 mmol, 1.00 equiv), 3,4-dihydro-2H-pyran (3.15 g, 37.45 mmol, 4.99 equiv) and toluenesulfonic acid (258 mg, 1.50 mmol, 0.20 equiv) in tetrahydrofuran (100 mL) was stirred at 80° C. for 8 h. The reaction mixture was cooled to room temperature and then diluted with H2O. The pH value of the solution was adjusted to 7 with saturated sodium bicarbonate solution. The resulting solution was extracted with 3×80 mL of ethyl acetate. The combined organic layers were washed with 1×80 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-25% of ethyl acetate in petroleum ether to give 1.5 g (55%) of (R/S) ethyl 5-iodo-3-methyl-1-(oxan-2-yl)-1H-pyrazole-4-carboxylate as a yellow oil. 1H-NMR (300 MHz, DMSO-d6): δ 5.45 (dd, J=9.9 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.88-3.84 (m, 1H), 3.69-3.60 (m, 1H), 2.49 (s, 3H), 1.95-1.75 (m, 2H), 1.65-1.45 (m, 4H), 1.29 (t, J=7.2 Hz, 3H) ppm. LCMS (method D, ESI): RT=1.55 min, m/z=365.0 [M+H]+.

Workup

  1. extractionThe resulting solution was extracted with 3×80 mL of ethyl acetate
  2. washThe combined organic layers were washed with 1×80 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified on a silica gel column
  6. washeluted with 0-25% of ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-51dfbd28a1724c5db7aa296eb5a446f4
Source dataset
uspto-grants-2015_02
Patent number
US08952026B2

Reaction notes

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