Potassium Carbonate → 2-Methyl-2-(3-pyridin-3-yl-phenoxy)-propionic acid methyl ester

HRID 1269494Notes

Reaction equation

HRID 1269494 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=2)[CH:2]=1.Br[C:15]([CH3:21])([CH3:20])[C:16]([O:18][CH3:19])=[O:17].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Cl-].[Na+].O>[CH3:19][O:18][C:16](=[O:17])[C:15]([CH3:21])([O:13][C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:8]=1)[CH3:20]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 90097Methyl 2-bromo-2-methylpropionateHCID 129379483-(Pyridin-3-yl)phenol

Product 1

HCID 688829912-Methyl-2-(3-pyridin-3-yl-phenoxy)-propionic acid methyl esterYield 80.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
93 °C

Procedure

A mixture of 3-pyridin-3-yl-phenol (0.86 g, 5.0 mmol), methyl 2-bromoisobutyrate (3.60 g, 20.0 mmol), and K2CO3 (2.76 g, 20.0 mmol) in anhydrous DMF (10 mL) was heated at 93° C. under nitrogen for 3 h. After cooling, brine (40 mL) was added and the mixture was extracted with ethyl acetate (50 mL). The separated organic layer was washed with brine, filtered, and concentrated. The oil residue was taken up in 10 mL of 3 M HCl, stirred for 10 min, diluted with brine (10 mL), and extracted with ethyl acetate (2×30 mL). The separated aqueous layer was cooled in ice/water bath, adjusted to pH 10 with solid Na2CO3, and extracted with ethyl acetate (2×40 mL). The organic extract was dried over sodium sulfate and concentrated to afford 1.09 g (80%) of 2-methyl-2-(3-pyridin-3-yl-phenoxy)-propionic acid methyl ester as a yellow oil: 1H NMR (CDCl3) δ 1.62 (s, 6H), 3.79 (s, 3H), 6.82 (dd, 1H), 7.08 (s, 1H), 7.20 (d, 1H), 7.38 (m, 2H), 7.81 (d, 1H), 8.59 (d, 1H), 8.80 (s, 1H); MS m/z (relative intensity) 271 (M+, 20), 212 (30), 171 (100).

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with ethyl acetate (50 mL)
  3. washThe separated organic layer was washed with brine
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additiondiluted with brine (10 mL)
  7. extractionextracted with ethyl acetate (2×30 mL)
  8. temperatureThe separated aqueous layer was cooled in ice/water bath
  9. extractionextracted with ethyl acetate (2×40 mL)
  10. extractionThe organic extract
  11. dry with materialwas dried over sodium sulfate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4d5540e595d74da4a3427d9e36b6fc7b
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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