Dimethylformamide → HCID 86713784, compound

HRID 521842Notes

Reaction equation

HRID 521842 reaction equation
[CH2:1]([O:4][CH:5]([C:10]1[N:11]([CH3:18])[N:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16])[CH2:6][C:7]([OH:9])=O)[CH:2]=[CH2:3].[C:19](Cl)(=O)[C:20](Cl)=O.CN(C=O)C.C([Sn](CCCC)(CCCC)CCCC)=C>C(Cl)Cl>[CH2:1]([O:4][CH:5]([C:10]1[N:11]([CH3:18])[N:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16])[CH2:6][C:7](=[O:9])[CH:19]=[CH2:20])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81998TributylvinyltinHCID 86713785HCID 86713785, compound

Product 1

HCID 86713784HCID 86713784, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-allyloxy-3-(2-methyl-4-nitro-pyrazol-3-yl)propanoic acid (4.33 g, 17 mmol) in DCM (48 mL) at 0° C. under nitrogen was added oxalyl chloride (4.37 mL, 51 mmol) followed by the cautious addition of DMF (0.05 mL) to initiate the acylation. The reaction mixture was stirred at room temperature for 3 hr and concentrated under reduced pressure. The residue was dissolved in DME (28 mL), vinyltributyltin (2.48 mL, 8.50 mmol) added and the mixture degassed with nitrogen for 30 min. trans-Benzyl(chloro)-bis(triphenylphosphine)palladium(II) (129 mg, 0.17 mmol) was added and degassing continued for 10 min. The reaction mixture was heated to 65° C. for 1 hr and cooled to room temperature. Concentration under reduced pressure and purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 5-(allyloxy)-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)pent-1-en-3-one as a yellow syrup (2.76 g, 61%). A solution of this syrup (250 mg, 0.94 mmol) in toluene (90 mL) was degassed with nitrogen for 30 min at 35° C. Zhan 1B catalyst (26 mg, 0.04 mmol) dissolved in toluene (2 mL) was added to the reaction mixture and degassing continued for 15 min. After stirring at 35° C. for 1 h, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-(2-methyl-4-nitro-pyrazol-3-yl)-3,7-dihydro-2H-oxepin-4-one as a colourless solid (107 mg, 30% over three steps). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 6.44 (ddd, J=12.8, 3.4, 2.3 Hz, 1H), 6.15 (m, 1H), 6.01 (dd, J=11.1, 3.4 Hz, 1H), 4.72 (ddd, J=19.8, 3.4, 1.7 Hz, 1H), 4.61 (ddd, J=19.6, 2.4 Hz, 1H), 4.08 (s, 3H), 3.20-3.12 (m, 2H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DME (28 mL)
  3. additionwas added
  4. customdegassing
  5. waitcontinued for 10 min
  6. temperatureThe reaction mixture was heated to 65° C. for 1 hr
  7. temperaturecooled to room temperature
  8. concentrationConcentration
  9. customunder reduced pressure and purification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-1ce4532e1ad24ffe9504af0ded0d58d3
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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