Dimethyl Sulfide → Methyl 2-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-amino}ethoxy)-3-(propan-2-yloxy)benzoate

HRID 577564Notes

Reaction equation

HRID 577564 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[C:6]([O:15][CH2:16][CH:17]=C)=[C:7]([CH:12]=[CH:13][CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])[CH3:3].CSC.Cl.[NH2:23][CH2:24][C:25]1[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=1[CH3:31].C([BH3-])#N.[Na+]>ClCCl.CO>[CH3:31][C:30]1[CH:29]=[C:28]([CH3:32])[NH:27][C:26](=[O:33])[C:25]=1[CH2:24][NH:23][CH2:17][CH2:16][O:15][C:6]1[C:5]([O:4][CH:2]([CH3:1])[CH3:3])=[CH:14][CH:13]=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

7

Reactant 4

HCID 1068Dimethyl SulfideHCID 5003444Sodium cyanoborohydrideHCID 438104513-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one hydrochlorideHCID 86723788Methyl 3-(propan-2-yloxy)-2-(prop-2-en-1-yloxy)benzoate

Product 1

HCID 86723789Methyl 2-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-amino}ethoxy)-3-(propan-2-yloxy)benzoateYield 11.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Ozone was bubbled through a cooled (−78° C.) solution of methyl 3-(propan-2-yloxy)-2-(prop-2-en-1-yloxy)benzoate (123d, 438.1 mg, 1.75 mmol) in dichloromethane (17.5 mL) until a persistent violet-blue color was obtained (about 5 minutes). Nitrogen was bubbled into the solution for 3 minutes, causing the color to fade, then dimethyl sulfide (1.0 mL, 13.5 mmol) was added and the mixture allowed to warm to room temperature for one hour. The solvents were evaporated and the residue partitioned between sodium carbonate solution (sat., aq., 10 mL) and ethyl acetate (2×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under vacuum to give the crude residue. This crude aldehyde was dissolved in methanol (10.0 mL) and treated with 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one hydrochloride (Cpd V, 334 mg, 1.87 mmol) at room temperature for five minutes, then sodium cyanoborohydride (332 mg, 4.50 mmol) was added and the mixture stirred at room temperature for 14.5 hours. The solvents were evaporated under vacuum and the residue partitioned between deionized water (10 mL) and ethyl acetate (2×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, concentrated under vacuum, and purified by column chromatography (EtOH+5% NH4OH in ethyl acetate) to give methyl 2-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]amino}ethoxy)-3-(propan-2-yloxy)benzoate (123e, 76 mg, 11% yield) as a colorless glass.

Workup

  1. customOzone was bubbled through
  2. customwas obtained (about 5 minutes)
  3. customNitrogen was bubbled into the solution for 3 minutes
  4. customThe solvents were evaporated
  5. customthe residue partitioned between sodium carbonate solution (sat., aq., 10 mL) and ethyl acetate (2×20 mL)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto give the crude residue
  10. customThe solvents were evaporated under vacuum
  11. customthe residue partitioned between deionized water (10 mL) and ethyl acetate (2×20 mL)
  12. dry with materialThe combined organic extracts were dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under vacuum
  15. custompurified by column chromatography (EtOH+5% NH4OH in ethyl acetate)

Sources & evidence

ORD record
ord-229146136b494f9d951b6dbfadb8080e
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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