1,2-Dichloroethane → ((R)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate

HRID 571174Notes

Reaction equation

HRID 571174 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][CH:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[OH:10].[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C@@H:34]([CH3:38])[C:35](O)=[O:36])[CH:28]=[CH:27]2.C(Cl)CCl.O>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([CH:34]([CH3:38])[C:35]([O:10][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[CH2:8][C:7]1[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=1[Cl:21])=[O:36])[CH:28]=[CH:27]2

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 962WaterHCID 169118Naproxen, (-)-HCID 670959732-(3,5-Dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol

Product 1

HCID 71092640((R)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoateYield 99%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol (50 g, 152 mmol), (R)-2-(6-methoxynaphthalen-2-yl)propanoic acid (38.6 g, 168 mmol), DMAP (20.5 g, 168 mmol), and EDC (43.8 g, 229 mmol) were dissolved in DMF (300 ml), and the reaction mixture was stirred at RT for 2 hours. Thereafter, water (500 ml) was added, and the solution stirred till complete precipitation occurs. The solid was filtered and dissolved in DCM (500 ml). The organic solution was washed with aqueous HCl 1N (2×500 ml), saturated aqueous NaHCO3 solution (500 ml) and dried over Na2SO4. The solvent was evaporated under vacuum and the solid residue sonicated in EtOH (300 ml) and triturated for 1 hour. The resulting precipitate was collected by filtration and dried under vacuum at 40° C. for 4 h to give 79 g (99% yield) of the title compound, as diastereoisomeric mixture.

Workup

  1. stirringthe solution stirred till complete precipitation
  2. filtrationThe solid was filtered
  3. dissolutiondissolved in DCM (500 ml)
  4. washThe organic solution was washed with aqueous HCl 1N (2×500 ml), saturated aqueous NaHCO3 solution (500 ml)
  5. dry with materialdried over Na2SO4
  6. customThe solvent was evaporated under vacuum
  7. customthe solid residue sonicated in EtOH (300 ml)
  8. customtriturated for 1 hour
  9. filtrationThe resulting precipitate was collected by filtration
  10. customdried under vacuum at 40° C. for 4 h

Sources & evidence

ORD record
ord-ae79dc398afd4cebba18f65923c80d01
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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