Hydrochloric Acid → 2-(2,3-Dihydro-2-oxo-3-benzofuranyl)acetic acid benzyl ester

HRID 1723181Notes

Reaction equation

HRID 1723181 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[O:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:15][C:14]1=[O:22].Br[CH2:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].[Cl-].[NH4+].Cl>O1CCCC1.CCCCCC.CN(P(N(C)C)(N(C)C)=O)C>[CH2:28]([O:27][C:25](=[O:26])[CH2:24][CH:15]1[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:13][C:14]1=[O:22])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 62576Benzyl bromoacetateHCID 683822(3H)-BenzofuranoneHCID 178418339Butyllithium

Product 1

HCID 143035372-(2,3-Dihydro-2-oxo-3-benzofuranyl)acetic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-60 °C

Procedure

A mixture of 7.53 g of diisopropylamine in 150 ml of anhydrous tetrahydrofuran is cooled under a stream of nitrogen to -60° C. 46.6 ml of a 1.6M solution of n-butyllithium in hexane is added dropwise at this temperature. When the addition is complete, the temperature of the reaction medium is allowed to rise to 5° C., the mixture is stirred for 10 minutes at this temperature and cooled to -80° C. and a solution of 10 g of 2,3-dihydro-2-benzofuranone in 150 ml of anhydrous tetrahydrofuran is added dropwise. The mixture is maintained for 10 minutes at -80° C. and then for 10 minutes at -60° C. It is cooled again to -80° C. and a solution of 18.8 g of benzyl bromoacetate in 16.05 g of hexamethylphosphorotriamide is added. The temperature is allowed to rise to 20° C., and the reaction mixture is stirred for 1 hour at this temperature and hydrolyzed at 0° C. using 26 ml of saturated ammonium chloride solution. The medium is then poured into 2.5 l of 1% strength hydrochloric acid solution. The precipitate is filtered off and dissolved in 200 ml of benzene, the organic phase is washed with water and dried over anhydrous sodium sulfate and the solvent is evaporated off. The residue is recrystallized in petroleum ether.

Workup

  1. additionWhen the addition
  2. customto rise to 5° C.
  3. temperaturecooled to -80° C.
  4. temperatureThe mixture is maintained for 10 minutes at -80° C.
  5. waitfor 10 minutes at -60° C
  6. temperatureIt is cooled again to -80° C.
  7. customto rise to 20° C.
  8. stirringthe reaction mixture is stirred for 1 hour at this temperature and hydrolyzed at 0° C.
  9. filtrationThe precipitate is filtered off
  10. dissolutiondissolved in 200 ml of benzene
  11. washthe organic phase is washed with water
  12. dry with materialdried over anhydrous sodium sulfate
  13. customthe solvent is evaporated off
  14. customThe residue is recrystallized in petroleum ether

Sources & evidence

ORD record
ord-f556c9200a93458a8b8d4249963e3b18
Source dataset
uspto-grants-1989_08
Patent number
US04859700

Reaction notes

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