Sodium Hydroxide → N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-3-ethoxy-6-hydroxy-N-(2-hydroxyethyl)-2-methylbenzamide

HRID 577550Notes

Reaction equation

HRID 577550 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([CH3:14])=[C:6]([C:10]([OH:13])=[CH:11][CH:12]=1)[C:7]([OH:9])=O)[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:27]([O:34][C:35]1[C:40]([CH2:41][NH:42][CH2:43][CH2:44][OH:45])=[C:39]([CH3:46])[CH:38]=[C:37]([CH3:47])[N:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[OH-].[Na+]>C1COCC1.C(OCC)(=O)C>[CH2:27]([O:34][C:35]1[C:40]([CH2:41][N:42]([CH2:43][CH2:44][OH:45])[C:7](=[O:9])[C:6]2[C:10]([OH:13])=[CH:11][CH:12]=[C:4]([O:3][CH2:1][CH3:2])[C:5]=2[CH3:14])=[C:39]([CH3:46])[CH:38]=[C:37]([CH3:47])[N:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 867236942-(((2-(Benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)amino)ethanolHCID 867237773-Ethoxy-6-hydroxy-2-methylbenzoic acid

Product 1

HCID 86723778N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-3-ethoxy-6-hydroxy-N-(2-hydroxyethyl)-2-methylbenzamideYield 69%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-ethoxy-6-hydroxy-2-methylbenzoic acid (114d, 0.168 g, 0.856 mmol) in THF (4.0 mL) was added 1,1′-carbonyldiimidazole (0.155 g, 0.91 mmol), and the reaction was stirred at 60° C. for 3 hours. The reaction mixture was allowed to cool to room temperature, and 2-({[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}amino)ethanol (Cpd KK, 330 mg, 1.10 mmol) was added. Heating was then continued at 60° C. for 16 hour. The reaction mixture was cooled to room temperature, and 10M NaOH (0.3 mL) was added. The reaction mixture was stirred at room temperature for 1 hour and was then poured into ethyl acetate and washed with 1M KH2PO4 and water. The organic layer was concentrated and purified by column chromatography (0-80% ethyl acetate/dichloromethane) to give N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-3-ethoxy-6-hydroxy-N-(2-hydroxyethyl)-2-methylbenzamide (114e, 0.274 g, 69% yield) as a white solid.

Workup

  1. temperatureto cool to room temperature
  2. temperatureHeating
  3. waitwas then continued at 60° C. for 16 hour
  4. temperatureThe reaction mixture was cooled to room temperature
  5. stirringThe reaction mixture was stirred at room temperature for 1 hour
  6. washwashed with 1M KH2PO4 and water
  7. concentrationThe organic layer was concentrated
  8. custompurified by column chromatography (0-80% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-95090a9523e846f28c4e77f5d5200e5f
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

Loading…