Sodium Hydroxide → 5-(cyclopentylmethoxy)pyridazin-3(2H)-one

HRID 2381355Notes

Reaction equation

HRID 2381355 reaction equation
Cl[C:2]1[C:3](=[O:15])[NH:4][N:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[OH-].[Na+].[H][H]>[Pd].O>[CH:10]1([CH2:9][O:8][C:7]2[CH:6]=[N:5][NH:4][C:3](=[O:15])[CH:2]=2)[CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 579191644-chloro-5-(cyclopentylmethoxy)pyridazin-3(2H)-one2×HCID 178418361HCID 178418361, compound

Product 1

HCID 668751985-(cyclopentylmethoxy)pyridazin-3(2H)-oneYield 78.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

A pressure vial containing a mixture of 4-chloro-5-cyclopentylmethoxy-2H-pyridazin-3-one (Intermediate 60, 0.75 g, 3.27 mmol), water (12 mL), and a 2N aqueous sodium hydroxide solution (2.1 mL) was treated with 10% palladium on carbon (75.1 mg, 10% weight of 4-chloro-5-cyclopentylmethoxy-2H-pyridazin-3-one). The reaction was then pressurized with hydrogen (40 psi), where it shook overnight. The resulting reaction mixture was removed from the hydrogenator and then warmed with a heat gun and quickly filtered through filter paper. The filter cake was rinsed with warm water and methylene chloride. The filtrate was filtered through filter paper to remove some residual catalyst and washed with methylene chloride. The filtrate was concentrated in vacuo to remove organics. Upon concentrating the aqueous layer was acidified with a 1N aqueous hydrochloric acid solution. The resulting precipitate was collected by filtration, rinsed with water and then dried in vacuo to afford 5-cyclopentylmethoxy-2H-pyridazin-3-one (499.6 mg, 78%) as an off-white solid; ES+-HRMS m/e calcd for C10H14N2O2 [M+H+] 195.1128, found 195.1128. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23-1.38 (m, 2H), 1.46-1.67 (m, 4H), 1.68-1.82 (m, 2H), 2.23-2.34 (m, 1H), 3.87 (d, J=7.0 Hz, 2H), 6.17 (s, 1H), 7.65 (d, J=2.6 Hz, 1H), 12.61 (br s, 1H).

Workup

  1. additionA pressure vial containing
  2. customThe resulting reaction mixture
  3. customwas removed from the hydrogenator
  4. temperaturewarmed with a heat gun
  5. filtrationquickly filtered
  6. filtrationthrough filter paper
  7. washThe filter cake was rinsed with warm water and methylene chloride
  8. filtrationThe filtrate was filtered
  9. filtrationthrough filter paper
  10. customto remove some residual catalyst
  11. washwashed with methylene chloride
  12. concentrationThe filtrate was concentrated in vacuo
  13. customto remove organics
  14. concentrationUpon concentrating the aqueous layer
  15. filtrationThe resulting precipitate was collected by filtration
  16. washrinsed with water
  17. customdried in vacuo

Sources & evidence

ORD record
ord-28728b3fb0de483e859e2d325f1812e4
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…