Imidazole → (+/-)-2-(Tert-butyldimethylsilyloxy)-3-phenylpropanoic acid

HRID 2075358Notes

Reaction equation

HRID 2075358 reaction equation
[OH:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].N1C=CN=C1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[Si:18]([O:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 3848(+-)-3-Phenyllactic acidHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 19765118(+/-)-2-(Tert-butyldimethylsilyloxy)-3-phenylpropanoic acidYield 40%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(±)-2-Hydroxy-3-phenylpropanoic acid (Sigma, 3.0 g, 18 mmol) was dissolved in 13 mL of DMF and chilled to 0° C. Imidazole (2.5 g, 36 mmol) and tert-butyldimethylsilylchloride (10 g, 69 mmol) were added. The mixture was allowed to warm to room temperature. After 12 hours, the mixture was diluted with 450 mL of 1:1 EtOAc:hexanes. The mixture was washed with 300 mL of 1M citric acid, 300 mL of water, and 150 mL of sat. Na2SO4, and the organic layer was evaporated. The residue was taken up in 170 mL of MeOH. The resulting mixture was chilled to 0° C. and potassium carbonate (5.7 g, 42 mmol) and 60 mL of water were added. The mixture was warmed to room temperature and stirred for 4 hours. The solvent was evaporated under reduced pressure. The residue was taken up in 5 mL of water and 1 M citric acid was added until the mixture reached pH 4.0. The mixture was extracted with EtOAc (3×100 mL), and the combined organic extracts were dried over MgSO4. The mixture was filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with a gradient of 10% to 30% EtOAc in hexanes) to afford (±)-2-(tert-butyldimethylsilyloxy)-3-phenylpropanoic acid (2.0 g, 40%) as a clear oil. 1H NMR (400 MHz, CDCl3): ppm 7.49-7.37 (m, 5H), 4.60 (dd, J=3.7 Hz, 7.6 Hz, 1H), 3.30 (dd, J=3.7 Hz, 13.7 Hz, 1H), 3.12 (dd, J=7.8 Hz, 13.6 Hz, 1H), 1.03 (s, 9H), 0.12 (s, 3H), 0.00 (s, 3H). Carboxyl H was not detected.

Workup

  1. temperatureto warm to room temperature
  2. washThe mixture was washed with 300 mL of 1M citric acid, 300 mL of water, and 150 mL of sat. Na2SO4
  3. customthe organic layer was evaporated
  4. temperatureThe resulting mixture was chilled to 0° C.
  5. temperatureThe mixture was warmed to room temperature
  6. customThe solvent was evaporated under reduced pressure
  7. addition1 M citric acid was added until the mixture
  8. extractionThe mixture was extracted with EtOAc (3×100 mL)
  9. dry with materialthe combined organic extracts were dried over MgSO4
  10. filtrationThe mixture was filtered
  11. customevaporated under reduced pressure
  12. customThe residue was purified by flash chromatography on silica gel (
  13. washeluting with a gradient of 10% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c8a901d47ab641de8a5642b42c5b6ab1
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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