Citric Acid → Ethyl 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate

HRID 1040332Notes

Reaction equation

HRID 1040332 reaction equation
Cl.Cl[CH2:3][CH2:4][CH2:5][N:6]([CH3:8])[CH3:7].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:27]=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:25]=[CH:24][C:23]=2[C:33]2[C:38]([O:39][CH3:40])=[CH:37][CH:36]=[CH:35][C:34]=2[O:41][CH3:42])=[CH:18][C:17]=1[OH:43].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:27]=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:25]=[CH:24][C:23]=2[C:33]2[C:38]([O:39][CH3:40])=[CH:37][CH:36]=[CH:35][C:34]=2[O:41][CH3:42])=[CH:18][C:17]=1[O:43][CH2:3][CH2:4][CH2:5][N:6]([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 66720714Ethyl 6-(4-chloro-3-hydroxyphenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate

Product 1

HCID 66720729Ethyl 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylateYield 91.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add 0.257 g (2.11 mmol) of 3-chloro-N,N-dimethylpropane-1-amine hydrochloride and 3.40 g (1.34 mmol) of caesium carbonate to a solution of 0.5 g (1.21 mmol) of ethyl 6-(4-chloro-3-hydroxyphenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate in 20 mL of anhydrous DMF under argon. Stir the reaction mixture for 15 min at RT then heat for 2 h at 80° C. After cooling to RT, add 1 mL of an aqueous solution of citric acid at 5% and concentrate the whole under reduced pressure. Take up the residue in 50 mL of EtOAc and wash with 10 mL of a 5% solution of Na2CO3 and then 10 mL of water. After drying over Na2SO4 and concentration under reduced pressure, purify the residue by silica gel column chromatography, eluting with a DCM/methanol gradient from 1 to 15% of methanol. After concentration under reduced pressure, we obtain 0.55 g of ethyl 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate in the form of oil.

Workup

  1. temperaturethen heat for 2 h at 80° C
  2. temperatureAfter cooling to RT
  3. concentrationconcentrate the whole under reduced pressure
  4. washwash with 10 mL of a 5% solution of Na2CO3
  5. dry with materialAfter drying over Na2SO4 and concentration under reduced pressure
  6. custompurify the residue by silica gel column chromatography
  7. washeluting with a DCM/methanol gradient from 1 to 15% of methanol
  8. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-ea9de0692ef340e595b423bd9bfb996b
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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