Sodium Carbonate → 2-Methyl-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-one

HRID 521831Notes

Reaction equation

HRID 521831 reaction equation
[CH3:1][N:2]1[C:6]([CH:7]2[O:14][C:11]3([CH2:13][CH2:12]3)[CH2:10][CH:9]([CH3:15])[O:8]2)=[C:5]([N+:16]([O-:18])=[O:17])[CH:4]=[N:3]1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:15][CH:9]1[CH2:10][C:11](=[O:14])[CH2:13][CH2:12][CH:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][C:5]=2[N+:16]([O-:18])=[O:17])[O:8]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 867137731-Methyl-5-(5-methyl-6,8-dioxaspiro[2.5]octan-7-yl)-4-nitro-pyrazole

Product 1

HCID 867137742-Methyl-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-oneYield 75%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-methyl-5-(5-methyl-6,8-dioxaspiro[2.5]octan-7-yl)-4-nitro-pyrazole (1.0 g, 3.95 mmol) in DCM (20 mL) at −78° C. was added titanium tetrachloride (6.6 mL, 59.3 mmol) dropwise. Halfway through the addition, the reaction mixture became harder to stir so more DCM (10 mL) was added. The brown slurry was warmed to 0° C. and stirred for 1 hr. Solid sodium carbonate (5 g) was cautiously added followed by saturated aqueous NaHCO3 (100 mL) and DCM (100 mL). The organic layer was washed with saturated aqueous NaHCO3, (100 mL) and brine (100 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-methyl-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-one as a colourless solid (749 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 5.69 (dd, J=11.0, 2.4 Hz, 1H), 4.21-4.14 (m, 1H), 4.01 (s, 3H), 3.07-2.97 (m, 1H), 2.79-2.63 (m, 3H), 2.19-2.07 (m, 1H), 2.07-1.91 (m, 1H), 1.30 (d, J=6.2 Hz, 3H).

Workup

  1. additionHalfway through the addition
  2. additionwas added
  3. washThe organic layer was washed with saturated aqueous NaHCO3, (100 mL) and brine (100 mL)
  4. customseparated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-caba2c62d3fd4b6d814ed0e5cbd6e3d5
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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