Hydrogen Peroxide → HCID 67288166, compound

HRID 922061Notes

Reaction equation

HRID 922061 reaction equation
[CH3:1][C:2]([CH3:25])([CH3:24])[CH2:3][CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:10]([CH:22]=[CH2:23])=[N:11][C:12]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[CH:13][C:14]=1[CH3:15])=[O:8].[OH-:26].[Na+].OO>C1COCC1>[CH3:1][C:2]([CH3:25])([CH3:24])[CH2:3][CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:10]([CH:22]([OH:26])[CH3:23])=[N:11][C:12]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[CH:13][C:14]=1[CH3:15])=[O:8]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 67287555HCID 67287555, compound

Product 1

HCID 67288166HCID 67288166, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 750 mg, (2.17 mmol) N-(4,4-dimethylpentyl)-4-methyl-6-morpholino-2-vinyl-pyridine-3-carboxylic acid amide (synthesized according to the methods described for example 9) in THF (10 ml) was added dropwise 730 μl (7.6 mmol) at 0° C. and the resulting mixture was stirred at RT for 16 h. The reaction mixture was cooled to 0° C. and a 1N aq. NaOH sol (4 ml) was added dropwise over a period of 0.5 h, followed by the addition of H2O2 (30% in water, 4 ml). Then the reaction mixture was stirred at RT for 4 h and was then extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. After CC (hexane/EtOAc 3:7) a mixture of N-(4,4-dimethylpentyl)-2-(2-hydroxyethyl)-4-methyl-6-morpholino-pyridine-3-carboxylic acid amide and N-(4,4-dimethylpentyl)-2-(1-hydroxyethyl)-4-methyl-6-morpholino-pyridine-3-carboxylic acid amide was obtained. This mixture was dissolved in THF (6 ml) and benzene (6 ml) and 24 mg, 0.0716 mmol) TBAHS was added at RT followed by the addition of a 25% aq. NaOH sol (6 ml) and 0.450 μl (7.16 mmol) iodomethane. Then the reaction mixture was slowly heated to 70° C. and stirred at the same temperature for 3 h. The additional 0.450 μl (7.16 mmol) iodomethane was added and stirring was continued at 70° C. for another 3 h. Then the organic layer was separated and the aq. layer was extracted with EtOAc. The combined organic layer was washed with water, and brine, dried over Na2SO4 and concentrated in vacuo. Purification of this residue by CC (hexane/EtOAc 3:2) provided 60 mg (0.16 mmol, 6%) N-(4,4-Dimethyl-pentyl)-2-(2-methoxy-ethyl)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 358). [M+H]+ 377.3

Workup

  1. additionwas added dropwise 730 μl (7.6 mmol) at 0° C.
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. stirringThen the reaction mixture was stirred at RT for 4 h
  4. extractionwas then extracted with EtOAc
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. additionAfter CC (hexane/EtOAc 3:7) a mixture of N-(4,4-dimethylpentyl)-2-(2-hydroxyethyl)-4-methyl-6-morpholino-pyridine-3-carboxylic acid amide

Sources & evidence

ORD record
ord-ddf1a299ec4f40e185ba12e8aa201cac
Source dataset
uspto-grants-2016_03
Patent number
US09278103B2

Reaction notes

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