Dimethyl Sulfoxide → 5-azido-1-(1-ethyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol

HRID 1915807Notes

Reaction equation

HRID 1915807 reaction equation
[N:1]([CH:4]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6][CH:5]1[OH:11])=[N+:2]=[N-:3].Cl[C:13]1[N:17]([CH3:18])[N:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20].[F-].[K+].O.[CH3:25]S(C)=O>>[N:1]([CH:4]1[CH2:10][CH2:9][N:8]([C:13]2[N:17]([CH2:18][CH3:25])[N:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[CH2:7][CH2:6][CH:5]1[OH:11])=[N+:2]=[N-:3]

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 522689Potassium FluorideHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 866799965-Azidoazepan-4-ol

Product 1

HCID 866800155-azido-1-(1-ethyl-4-nitro-1H-pyrazol-5-yl)azepan-4-olYield 53%

Conditions

Temperature
60 °C

Procedure

A solution of 5-azidoazepan-4-ol (2.5 g, 16.0 mmol) was dissolved in dry DMSO (20 mL) and 5-chloro-1-methyl-4-nitro-1H-pyrazole (2.70 g, 15.4 mmol) and potassium fluoride (3.71 g, 64 mmol) were added. The mixture was heated at 60° C. for 16 hr, allowed to cool to room temperature, poured into water (300 mL) and extracted into EtOAc (2×50 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 5-azido-1-(1-ethyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol as a yellow gum (2.5 g, 53%). 1H NMR (400 MHz, CDCl3) δ 8.18-7.95 (m, 1H), 4.16-4.07 (m, 2H), 3.80 (tt, J=9.1, 3.1 Hz, 1H), 3.67-3.59 (m, 1H), 3.42-3.18 (m, 4H), 2.51 (d, J=2.9 Hz, 1H), 2.24-2.12 (m, 2H), 2.07-1.87 (m, 2H), 1.46 (t, J=7.3 Hz, 3H).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted into EtOAc (2×50 mL)
  3. customThe combined organic layers were passed through a phase separation cartridge
  4. concentrationconcentrated under reduced pressure
  5. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-108f0cc87ba043e588e5278a9471e087
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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