Methanol → Methyl (2R)‐2‐{4‐[(5‐chloro‐3‐fluoropyridin‐2‐ yl)oxy]phenoxy}propanoate

HRID 2107516Notes

Reaction equation

HRID 2107516 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:21])[C:5]([O:8][C:9]2[CH:20]=[CH:19][C:12]([O:13][C@H:14]([CH3:18])[C:15](Cl)=[O:16])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:29][OH:30]>C1(C)C=CC=CC=1>[CH3:29][O:30][C:15](=[O:16])[C@H:14]([O:13][C:12]1[CH:11]=[CH:10][C:9]([O:8][C:5]2[C:4]([F:21])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)=[CH:20][CH:19]=1)[CH3:18]

Participants

5

Reactant 3

HCID 887MethanolHCID 8471TriethylamineHCID 15171159(R)(+)-2-[4-(5-chloro-3-fluoropyridin-2-yloxy)-phenoxy]-propionic acid chloride

Product 1

HCID 15592837Methyl (2R)‐2‐{4‐[(5‐chloro‐3‐fluoropyridin‐2‐ yl)oxy]phenoxy}propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 10.6 g (0.030 mol) of (R)(+)-2-[4-(5-chloro-3-fluoropyridin-2-yloxy)-phenoxy]-propionic acid chloride in 100 ml toluene is added slowly, while stirring into a solution of 4.9 ml (0.035 mol) of triethylamine and 2 ml (0.035mol) of methanol in 40 ml of toluene, that is cooled in an ice/bath. When everything is added, the ice-bath is removed and the reaction mixture is stirred for 3 hours at room temperature. The reaction mixture is then poured into ice-water and the organic material is extracted twice with ethyl acetate. The ethyl acetate layer is washed with a saturated salt solution, dried over magnesium sulfate, filtered and evaporated. The residue is purified by chromatography over a silicagel column with a hexane/ethyl acetate solution. After evaporation of the solvent, a clear oil, the above ester remains n35D 1.5859, [α]20D =+38.8±0.5 (2 % acetone).

Workup

  1. temperatureis cooled in an ice/bath
  2. additionWhen everything is added
  3. customthe ice-bath is removed
  4. additionThe reaction mixture is then poured into ice-water
  5. extractionthe organic material is extracted twice with ethyl acetate
  6. washThe ethyl acetate layer is washed with a saturated salt solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is purified by chromatography over a silicagel column with a hexane/ethyl acetate solution
  11. customAfter evaporation of the solvent

Sources & evidence

ORD record
ord-5e316ae3831b446db073991c3162335c
Source dataset
uspto-grants-1990_06
Patent number
US04935051

Reaction notes

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