Ethyl oxoacetate → Ethyl 2-(6-bromo-1-hydroxy-3-methylnaphthalen-2-yl)-2-hydroxyacetate

HRID 926182Notes

Reaction equation

HRID 926182 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[CH:7][C:6]([CH3:13])=[CH:5]2.[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[CH:15]=[O:16]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[C:7]([CH:15]([OH:16])[C:14]([O:18][CH2:19][CH3:20])=[O:17])[C:6]([CH3:13])=[CH:5]2

Participants

5

Reactant 2

HCID 70211Ethyl oxoacetateHCID 708356316-Bromo-3-methylnaphthalen-1-ol

Product 1

HCID 89676681Ethyl 2-(6-bromo-1-hydroxy-3-methylnaphthalen-2-yl)-2-hydroxyacetate

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of 6-bromo-3-methylnaphthalen-1-ol (3.79 g, 15.98 mmol) in anhydrous dichloromethane (150 mL) at −40° C. was added a 1M titanium(IV) chloride solution in dichloromethane (20.78 mL, 13.78 mmol) and stirred for 45 min. Ethyl glyoxalate (2.45 g, 23.97 mmol) dissolved in dichloromethane (10 mL) was added over 15 minutes and stirred for 1 hour at −40° C. The reaction was quenched by the addition of Rochelle's salt solution and stirred at room temperature for 2.5 hours. The resulting mixture was washed with water and aqueous layer back-extracted with dichloromethane (2×). The combined organic layer was dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 5 to 30% ethyl acetate/hexanes) to give the desired compound. LCMS-ESI− (m/z): [M−H]− calcd for C15H15BrO4: 338.18. Found: 338.8.

Workup

  1. additionwas added over 15 minutes
  2. stirringstirred for 1 hour at −40° C
  3. customThe reaction was quenched by the addition of Rochelle's salt solution
  4. stirringstirred at room temperature for 2.5 hours
  5. washThe resulting mixture was washed with water and aqueous layer
  6. extractionback-extracted with dichloromethane (2×)
  7. dry with materialThe combined organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash column chromatography (silica gel, 5 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-da80add707164de087afae8634c6b845
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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