Ethyl Acetoacetate → HCID 86744698, compound

HRID 1084445Notes

Reaction equation

HRID 1084445 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].C([Li])CCC.[CH3:17][N:18]1[C:27](/[CH:28]=[CH:29]/[CH:30]=[O:31])=[C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:38].[Cl-].[NH4+]>O1CCCC1.CCCCCC.C(OCC)(=O)C.O.C(OCC)C>[OH:31][CH:30](/[CH:29]=[CH:28]/[C:27]1[N:18]([CH3:17])[C:19](=[O:38])[C:20]2[C:25]([C:26]=1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8]

Participants

11

Reactant 5

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86744705HCID 86744705, compoundHCID 178418339Butyllithium

Product 1

HCID 86744698HCID 86744698, compoundYield 71%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A stirred suspension of sodium hydride (0.078 g; 80% dispersion in mineral oil) in dry tetrahydrofuran (10 ml) under an atmosphere of nitrogen and at -10° C. was treated with ethyl acetoacetate (0.312 g), dropwise, during 5 minutes. The mixture was stirred for 30 minutes and then it was treated with a solution of butyl lithium in hexane (1 ml; 2.5M) during a period of 5 minutes, whilst maintaining the temperature at -10° C. The mixture was stirred for a further period of 20 minutes at -10° C. and then treated with a solution of (E)-3-(2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-3-yl)propenal (0.34 g) in dry tetrahydrofuran (30 ml), dropwise, during 15 minutes at -10° C. The mixture was stirred at -10° C. for 2 hours and the resulting red-brown solution was treated with saturated aqueous ammonium chloride solution (15 ml) and then it was poured into a mixture of diethyl ether (75 ml) and water (50 ml). The organic phase was separated and the aqueous phase was extracted with diethyl ether (50 ml). The combined organic phases were washed with water (3×50 ml), dried over magnesium sulphate and evaporated, to give a yellow solid which was subjected to flash chromatography on silica gel, using ethyl acetate as eluent, to give ethyl (E)-5-hydroxy-7-(2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-3-yl)-3-oxohept-6-enoate (0.35 g) in the form of a yellow solid, m.p.148°-149° C.

Workup

  1. stirringThe mixture was stirred for a further period of 20 minutes at -10° C.
  2. waitdropwise, during 15 minutes at -10° C
  3. stirringThe mixture was stirred at -10° C. for 2 hours
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with diethyl ether (50 ml)
  6. washThe combined organic phases were washed with water (3×50 ml)
  7. dry with materialdried over magnesium sulphate
  8. customevaporated
  9. customto give a yellow solid which

Sources & evidence

ORD record
ord-dd04d1590b6b499fa5dceda515b01fc0
Source dataset
uspto-grants-1991_04
Patent number
US05004747

Reaction notes

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