Ethyl Acetate → 4-[6-(2,6-Diethyl-phenyl)-3-(2,2-dimethyl-morpholin-4-ylmethyl)-2-methyl-pyridin-4-yloxy]-2-hydroxy-benzamide

HRID 1392674Notes

Reaction equation

HRID 1392674 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[C:13]([CH2:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:16][CH3:17])[N:5]=[C:4]([CH3:18])[C:3]=1[CH2:19][N:20]1[CH2:25][CH2:24][O:23][C:22]([CH3:27])([CH3:26])[CH2:21]1.[OH:28][C:29]1[CH:37]=[C:36]([OH:38])[CH:35]=[CH:34][C:30]=1[C:31]([NH2:33])=[O:32].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN1CCCC1=O.[Cu].O>[CH2:16]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14][CH3:15])[C:8]=1[C:6]1[N:5]=[C:4]([CH3:18])[C:3]([CH2:19][N:20]2[CH2:25][CH2:24][O:23][C:22]([CH3:27])([CH3:26])[CH2:21]2)=[C:2]([O:38][C:36]2[CH:35]=[CH:34][C:30]([C:31]([NH2:33])=[O:32])=[C:29]([OH:28])[CH:37]=2)[CH:7]=1)[CH3:17]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 766012,4-DihydroxybenzamideHCID 596782124-[4-Chloro-6-(2,6-diethyl-phenyl)-2-methyl-pyridin-3-ylmethyl]-2,2-dimethyl-morpholine

Product 1

HCID 596782004-[6-(2,6-Diethyl-phenyl)-3-(2,2-dimethyl-morpholin-4-ylmethyl)-2-methyl-pyridin-4-yloxy]-2-hydroxy-benzamide

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-[4-chloro-6-(2,6-diethyl-phenyl)-2-methyl-pyridin-3-ylmethyl]-2,2-dimethyl-morpholine (30 mg, 0.08 mmol), 2,4-dihydroxy-benzamide (24 mg, 0.16 mmol), copper powder (10 mg) and K2CO3 (22 mg, 0.16 mmol) in 1-methyl-2-pyrrolidinone (1 mL) is heated at 150° C. overnight. After cooling, EtOAc (10 mL) and water (10 mL) are added to the mixture. The organic layer is separated, washed with brine (3×), dried (Na2SO4) and concentrated. The crude is purified by PTLC (1:1 Hexane/EtOAc) to give to give the title compound. 1H NMR (CDCl3) 12.41 (s, 1H), 7.35 (d, 2H), 7.23 (m, 1H), 7.10 (m, 2H), 6.63 (s, 1H), 6.51 (m, 2H), 5.85 (br, 2H), 3.72 (m, 2H), 3.56 (s, 2H), 2.74 (s, 3H), 2.41-2.30 (m, 6H), 1.20 (s, 6H), 1.76 (m, 2H), 1.01 (t, 6H).

Workup

  1. temperatureAfter cooling
  2. customThe organic layer is separated
  3. washwashed with brine (3×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude is purified by PTLC (1:1 Hexane/EtOAc)
  7. customto give

Sources & evidence

ORD record
ord-eca786cb8079415dbb54b6a3d0fcdd7b
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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