Sulfuric Acid → Ethyl 3-(4-hydroxyphenyl)-2-isopropoxypropanoate

HRID 1985261Notes

Reaction equation

HRID 1985261 reaction equation
[OH:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]2[O:11][C:10]([CH3:13])([CH3:12])[O:9][C:8]2=[O:14])=[CH:4][CH:3]=1.[CH2:17]([SiH](CC)CC)[CH3:18].OS(O)(=O)=O>C(Cl)Cl.CCO.Cl[Ti](Cl)(Cl)Cl>[CH2:17]([O:9][C:8](=[O:14])[CH:7]([O:11][CH:10]([CH3:13])[CH3:12])[CH2:6][C:5]1[CH:15]=[CH:16][C:2]([OH:1])=[CH:3][CH:4]=1)[CH3:18]

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 12052TriethylsilaneHCID 99208865-(4-Hydroxy-benzyl)-2,2-dimethyl-(1,3]dioxolan-4-one

Product 1

HCID 22926879Ethyl 3-(4-hydroxyphenyl)-2-isopropoxypropanoateYield 70%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of 5-(4-hydroxy-benzyl)-2,2-dimethyl-[1,3]dioxolan-4-one (0.20 g, 0.900 mmol) and triethylsilane (1.05 g, 9.0 mmol) in dry CH2Cl2 (10 mL) was treated dropwise with a 1 molar solution of TiCl4 in CH2Cl2 (0.90 mL, 0.900 mmol) under N2. The resultant red slurry was stirred at 0° C. for 15 minutes and then warmed to room temperature for 45 minutes. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried (Na2SO4) and the solvent removed in vacuo to afford 0.320 g of crude acid that was carried on as is. The oil was dissolved in EtOH (25 mL) and treated with conc. H2SO4 (1 mL) and then stirred at room temperature for 17 h under N2. The solvent was removed in vacuo and the oil extracted with EtOAc and water. The organic layer was dried (Na2SO4) and the solvent removed in vacuo to afford crude product that was purified by flash chromatography using 5:1 hexanes:acetone to give 0.158 g (70%) 3-(4-hydroxy-phenyl)-2-isopropoxy-propionic acid ethyl ester. Rf=0.48 (1:1 hexanes:acetone). 1H NMR (500 MHz, CDCl3) δ 7.10 (d, 2H, J=8.80 Hz), 6.73 (d, 2H, J=8.31 Hz), 4.79 (bs, 1H) 4.20-4.12 (m, 2H), 3.99 (dd, 1H, J=8.31 Hz, J=4.89 Hz), 3.49 (hp, 1H, J=5.87 Hz), 2.95-2.83 (m, 2H), 1.23 (t, 3H, J=6.85 Hz), 1.14 (d, 3H, J=6.36 Hz), 0.97 (d, 3H, J=6.36 Hz); MS (ES−) Calc'd for C14H19O4 (M−1) 251. Found m/z 251 (100%). 97.6% ee by chiral HPLC assay (Chiralcel OJ, 4.6×250 mm, 90/10 heptane/IPA eluent, 1 mL/min, 266 nm).

Workup

  1. temperaturewarmed to room temperature for 45 minutes
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customthe solvent removed in vacuo
  6. customto afford 0.320 g of crude acid that
  7. stirringstirred at room temperature for 17 h under N2
  8. customThe solvent was removed in vacuo
  9. extractionthe oil extracted with EtOAc and water
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. customthe solvent removed in vacuo
  12. customto afford crude product that
  13. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-4917cc101bd2426b95697128844aa6a2
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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