Hydrochloric Acid → (2RS,3RS)-3-(2-fluoropyridin-4-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionic acid

HRID 1610498Notes

Reaction equation

HRID 1610498 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH:8]([OH:29])[CH:9]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:17]=2)[C:10]([O:12]CC)=[O:11])[CH:5]=[CH:4][N:3]=1.[OH-].[Na+].Cl>CO>[F:1][C:2]1[CH:7]=[C:6]([CH:8]([OH:29])[CH:9]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:17]=2)[C:10]([OH:12])=[O:11])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22262212Ethyl 3-(2-fluoropyridin-4-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionate

Product 1

HCID 17862120(2RS,3RS)-3-(2-fluoropyridin-4-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionic acidYield 60.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of ethyl(2RS,3RS)-3-(2-fluoropyridin-4-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionate (3.8 g, 9.06 mmol, (2RS,3RS) form: (2RS,3SR) form=9:1) in methanol (20 ml) was added 2N aqueous sodium hydroxide solution (9.1 ml), 18.2 mmol), and the mixture was stirred at room temperature for 2 hrs. The reaction solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Recrystallization of the residue from ethyl acetate-hexane gave (2RS,3RS)-3-(2-fluoropyridin-4-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionic acid (2.14 g, 60%).

Workup

  1. extractionextracted with ethyl acetate (200 ml×2)
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. customRecrystallization of the residue from ethyl acetate-hexane

Sources & evidence

ORD record
ord-85a77d378e10490d9684f97ca7437001
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

Loading…