Diethyl Oxalate → Ethyl 2-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxyacetate

HRID 367342Notes

Reaction equation

HRID 367342 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11]1[CH:16]=[C:15](Br)[CH:14]=[CH:13][C:12]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:31](OCC)(=[O:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33].[BH4-].[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1.CCCCCC.O.C(O)(=O)C.C(O)C>[CH2:19]([O:18][C:12]1[CH:13]=[CH:14][C:15]([CH:31]([OH:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:16][C:11]=1[CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

11

Reactant 5

HCID 7268Diethyl OxalateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 23287828Benzyl 2-(2-benzyloxyethyl)-4-bromophenyl etherHCID 178418339Butyllithium

Product 1

HCID 23287822Ethyl 2-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxyacetateYield 78.3%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-95 °C

Procedure

Benzyl 2-(2-benzyloxyethyl)-4-bromophenyl ether (24.0 g) was dissolved in 200 ml of tetrahydrofuran, 47.0 ml of 1.57 M n-butyl lithium in hexane was added to the solution with stirring at -95° C., and the mixture was subjected to 15 minutes of reaction. The reaction solution was added to a solution of 10.8 g of diethyl oxalate in 300 ml of tetrahydrofuran with stirring at -95° C., and the resulting solution was subjected to 1 hour of reaction. Then, 200 ml of ethanol and 755 mg of sodium borohydride were added in that order. The reaction solution was stirred at -35° C. for 45 minutes, 4.70 ml of acetic acid was added, and the mixture was stirred for 15 minutes. Then, a solution of 6.9 g of sodium bicarbonate in 300 ml of water was added and then the mixture was concentrated under reduced pressure. The resulting concentrate was extracted with ethyl acetate, and the extract was washed with water and then dried over anhydrous magnesium sulfate. Thereafter, the solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel medium pressure liquid column chromatography (eluent: hexane/ethyl acetate=3/1) to give 19.9 g of ethyl 2-[4-benzyloxy-3-(2benzyloxyethyl)phenyl]-2-hydroxyacetate in an oily form.

Workup

  1. customthe mixture was subjected to 15 minutes of reaction
  2. stirringwith stirring at -95° C.
  3. customthe resulting solution was subjected to 1 hour of reaction
  4. stirringThe reaction solution was stirred at -35° C. for 45 minutes
  5. stirringthe mixture was stirred for 15 minutes
  6. concentrationthe mixture was concentrated under reduced pressure
  7. concentrationThe resulting concentrate
  8. extractionwas extracted with ethyl acetate
  9. washthe extract was washed with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThereafter, the solvent was evaporated under reduced pressure
  12. customthe resulting residue was purified by silica gel medium pressure liquid column chromatography (eluent: hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-1df11644ae2b4033999203099a84f5c3
Source dataset
uspto-grants-2000_10
Patent number
US06133266

Reaction notes

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