Methyl acetoacetate → HCID 131719005, compound

HRID 36919

Reaction equation

HRID 36919 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[CH2:11]([Li])CCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28](/[CH:29]=[CH:30]/[CH:31]=[O:32])=[C:27]([CH:33]([CH3:35])[CH3:34])[N:26]=[C:25]([O:36][CH3:37])[C:24]=2COC)=[CH:19][CH:18]=1.[O:41]1CCC[CH2:42]1>CCCCCC.CCOCC.[Cl-].[NH4+].[Cl-].[Zn+2].[Cl-]>[F:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:28](/[CH:29]=[CH:30]/[CH:31]([OH:32])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:27]([CH:33]([CH3:35])[CH3:34])[N:26]([CH3:11])[CH:25]([O:36][CH3:37])[C:24]=2[O:41][CH3:42])=[CH:21][CH:22]=1

Participants

10

Reactant 5

HCID 7757Methyl acetoacetateHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 19936689(E)-3-[4-(4-Fluorophenyl)-6-isopropyl-2-methoxy-3-methoxymethyl-pyridin-5-yl]-prop-2-enalHCID 178418339Butyllithium

Product 1

HCID 131719005HCID 131719005, compound

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8058HexaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

0.35 ml (3.3 mmol) of methyl acetoacetate are added dropwise under nitrogen to a suspension of 80 mg (3.4 mmol) of sodium hydride in 3 ml of dry tetrahydrofuran at -5° C. After 15 min, 2.3 ml (3.3 mmol) of 15% strength butyllithium in n-hexane and 3.3 ml (3.3 mmol) of a 1 molar zinc chloride solution in ether are added dropwise at the same temperature and the mixture is stirred for 15 min. 530 mg (1.5 mmol) of the compound from Example 10 dissolved in 8 ml of dry tetrahydrofuran are then added dropwise and the mixture is stirred at -5° C. for 30 min. The reaction solution is cautiously diluted with 100 ml of saturated aqueous ammonium chloride solution and the mixture is extracted three times with 100 ml of ether each time. The combined organic phases are washed twice with saturated sodium hydrogen carbonate solution and once with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo.

Workup

  1. additionare then added dropwise
  2. stirringthe mixture is stirred at -5° C. for 30 min
  3. extractionthe mixture is extracted three times with 100 ml of ether each time
  4. washThe combined organic phases are washed twice with saturated sodium hydrogen carbonate solution and once with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b62755906215485e999eb3fe515012ae
Source dataset
uspto-grants-1995_05
Patent number
US05418243

Linked notes

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