Water → 4-Iodo-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-pyrazole

HRID 2285188Notes

Reaction equation

HRID 2285188 reaction equation
[I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:14][CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1.O>CC#N>[I:1][C:2]1[CH:3]=[N:4][N:5]([CH2:14][CH2:15][CH2:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 770224-IodopyrazoleHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyran

Product 1

HCID 866871804-Iodo-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-pyrazoleYield 85.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 4-iodo-1H-pyrazole (2.0 g, 10.3 mmol) and Cs2CO3 (5.04 g, 15.5 mmol) in MeCN (28 mL) was added 2-(3-bromopropoxy)tetrahydro-2H-pyran (1.84 mL, 10.8 mmol) and the mixture stirred overnight. The crude reaction mixture was poured into water and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-80% EtOAc in cyclohexane, to give the title compound (2.95 g, 81%). 1H NMR (300 MHz, CDCl3): 150-1.58 (4H, m), 1.65-1.90 (2H, m), 2.12 (2H, qn, J=6.4 Hz), 3.35 (1H, dt, J=10.2, 5.9 Hz), 3.46-3.54 (1H, m), 3.73 (1H, dt, J=10.2, 5.9 Hz), 3.80-3.88 (1H, m), 4.26 (2H, td, J=6.9, 1.5 Hz), 4.54 (1H, dd, J=4.5, 3.1 Hz), 7.46 (1H, s), 7.50 (1H, s).

Workup

  1. customThe crude reaction mixture
  2. extractionextracted with EtOAc (×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-b4ad33e1c8ea4e3ead9d053dc3fdfb66
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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