Ethyl oxoacetate → HCID 89676580, compound

HRID 926134Notes

Reaction equation

HRID 926134 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:13])[C:5]2[C:10]([C:11]=1[CH3:12])=[CH:9][CH:8]=[CH:7][CH:6]=2.[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[CH:15]=[O:16]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[OH:16][CH:15]([C:3]1[C:2]([CH3:1])=[C:11]([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[OH:13])[C:14]([O:18][CH2:19][CH3:20])=[O:17]

Participants

5

Reactant 2

HCID 70211Ethyl oxoacetateHCID 15915434HCID 15915434, compound

Product 1

HCID 89676580HCID 89676580, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-40 °C

Procedure

To a solution of 3,4-dimethylnaphthalen-1-ol (3.18 g, 18.46 mmol) in dichloromethane (180 mL) at −40° C. was added a 1M solution of titanium tetrachloride in dichloromethane (18.46 mL, 18.46 mmol) over 10 minutes. In a separate flask, ethyl glyoxalate (2.26 g, 22.16 mmol) was heated at 100° C. for 45 minutes. The colorless oil was dissolved in dichloromethane (20 mL) and added to the reaction mixture over 10 minutes. The reaction mixture was stirred at −40° C. for 1.5 hours, then warmed to −25° C. over 30 minutes. The reaction mixture was quenched with acetic acid (5.8 mL). Acetonitrile (30 mL) was added and the reaction mixture was stirred for 5 minutes. The cold bath was removed and water (59 mL) was added and stirred for 15 minutes. The mixture was diluted with water and brine and extracted with dichloromethane (3×). The combined organic layer was dried (MgSO4), filtered, concentrated and purified twice by flash column chromatography (silica gel, 0 to 25% ethyl acetate/hexanes) to give ethyl 2-hydroxy-2-(1-hydroxy-3,4-dimethylnaphthalen-2-yl)acetate. LCMS-ESI− (m/z): [M−H]− calcd for C16H17O4: 273.31. Found: 272.8.

Workup

  1. additionadded to the reaction mixture over 10 minutes
  2. temperaturewarmed to −25° C. over 30 minutes
  3. customThe reaction mixture was quenched with acetic acid (5.8 mL)
  4. additionAcetonitrile (30 mL) was added
  5. stirringthe reaction mixture was stirred for 5 minutes
  6. customThe cold bath was removed
  7. additionwater (59 mL) was added
  8. stirringstirred for 15 minutes
  9. additionThe mixture was diluted with water and brine
  10. extractionextracted with dichloromethane (3×)
  11. dry with materialThe combined organic layer was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified twice by flash column chromatography (silica gel, 0 to 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8cd1b56faa094c1fa4f1c5e572acc0b4
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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