Cesium carbonate → 3-Hydroxy-2-methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-propionic acid methyl ester

HRID 2212566Notes

Reaction equation

HRID 2212566 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH:4]([CH3:14])[CH:5]([OH:13])[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.Cl[CH2:17][C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([CH3:28])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[CH3:1][O:2][C:3](=[O:15])[CH:4]([CH3:14])[CH:5]([OH:13])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[C:20]([CH3:28])[CH:19]=2)=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 115357194-(Chloromethyl)-2-methylquinolineHCID 623934773-Hydroxy-3-(4-hydroxy-phenyl)-2-methyl-propionic acid methyl ester

Product 1

HCID 695964113-Hydroxy-2-methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-propionic acid methyl esterYield 84.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The 3-hydroxy-3-(4-hydroxy-phenyl)-2-methyl-propionic acid methyl ester (0.24 g, 1.14 mmol) was combined with the 4-chloromethyl-2-methyl-quinoline (0.313 g, 1.37 mmol) and cesium carbonate (1.1 g, 3.42 mmol) in DMSO (5 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 18 h, filtered to remove the solids, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give a mixture of diasteromers. The product was purified by FCC on silica gel eluting with ethyl acetate:hexane (60:40, v: v) to give 3-hydroxy-2-methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-propionic acid methyl ester (0.352 g, 84%) as a glass. MS found: (M+H)+=366.

Workup

  1. filtrationfiltered
  2. customto remove the solids
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give
  8. additiona mixture of diasteromers
  9. customThe product was purified by FCC on silica gel eluting with ethyl acetate:hexane (60:40, v: v)

Sources & evidence

ORD record
ord-90c8813362684c10959d03daaddb5777
Source dataset
uspto-grants-2006_09
Patent number
US07102008B2

Reaction notes

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