Water → 1-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-iodo-1H-pyrazole

HRID 389441Notes

Reaction equation

HRID 389441 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.CS(O[CH:14]1[CH2:23][CH2:22][C:17]2([O:21][CH2:20][CH2:19][O:18]2)[CH2:16][CH2:15]1)(=O)=O.O>CN(C=O)C.CO>[O:18]1[C:17]2([CH2:22][CH2:23][CH:14]([N:6]3[CH:5]=[C:4]([I:3])[CH:8]=[N:7]3)[CH2:15][CH2:16]2)[O:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 962Water2×HCID 24758Sodium hydrideHCID 770224-IodopyrazoleHCID 149667411,4-Dioxaspiro(4.5)decan-8-yl methanesulfonate

Product 1

HCID 595411251-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-iodo-1H-pyrazoleYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent3×

Procedure

A suspension of sodium hydride (72.6 mg, 1.82 mmol) in DMF (1 mL); was cooled in an ice/water bath and treated with a solution of 4-iodopyrazole (242 mg, 1.21 mmol) in DMF (2 mL) added dropwise under an atmosphere of nitrogen in 5 min. After stirring in the cold for another 30 min, a solution of 1,4-dioxaspiro[4.5]dec-8-yl methanesulfonate (321 mg, 1.33 mmol) in DMF (2 mL) was added dropwise at 0° C. The mixture was warmed to RT and was then immersed in 150° C. oil bath and stirred for 2 h. The mixture was treated with water (15 mL), extracted with EtOAc (3×20 mL). The extracts were washed with water (3×15 mL), brine (15 mL), dried over MgSO4. After concentration in vacuo, a brown solid was obtained. It was dissolved in MeOH and after water was added, a solid formed, which was filtered off to give 266 mg (66%) of the title compound as a white crystalline solid. 1H NMR (400 MHz, CDCl3): δ 7.50 (s, 1 H), 7.49 (s, 1 H), 4.23 (tt, J=4.2, 11.2 Hz, 1 H), 2.34-2.20 (m, 1 H), 2.21-1.96 (m, 4 H), 1.95-1.81 (m, 2 H), 1.82-1.66 (m, 3 H), 1.33-1.22 (m, 2 H); MS (ESI): 334.96 [M+H]+; HPLC tR=3.26 min.

Workup

  1. temperaturewas cooled in an ice/water bath
  2. additionadded dropwise under an atmosphere of nitrogen in 5 min
  3. customwas then immersed in 150° C.
  4. stirringstirred for 2 h
  5. extractionextracted with EtOAc (3×20 mL)
  6. washThe extracts were washed with water (3×15 mL), brine (15 mL)
  7. dry with materialdried over MgSO4
  8. concentrationAfter concentration in vacuo
  9. customa brown solid was obtained
  10. customa solid formed
  11. filtrationwhich was filtered off

Sources & evidence

ORD record
ord-93f7041281e542e897e68f041a72c992
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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