Methyl acetoacetate → HCID 17821740, compound

HRID 1084884Notes

Reaction equation

HRID 1084884 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[CH:16]([C:19]1[C:24](/[CH:25]=[CH:26]/[CH:27]=[O:28])=[C:23]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[C:22]([CH2:36][O:37][C:38](=[O:44])[C:39]([CH3:43])([CH3:42])[CH2:40][CH3:41])=[C:21]([CH:45]([CH3:47])[CH3:46])[N:20]=1)([CH3:18])[CH3:17].[Cl-].[NH4+]>O1CCCC1.CCCCCC.[Br-].[Zn+2].[Br-]>[CH:16]([C:19]1[C:24](/[CH:25]=[CH:26]/[CH:27]([OH:28])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:23]([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[C:22]([CH2:36][O:37][C:38](=[O:44])[C:39]([CH3:42])([CH3:43])[CH2:40][CH3:41])=[C:21]([CH:45]([CH3:46])[CH3:47])[N:20]=1)([CH3:17])[CH3:18]

Participants

9

Reactant 5

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 20081775HCID 20081775, compoundHCID 178418339Butyllithium

Product 1

HCID 17821740HCID 17821740, compound

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-5 °C

Procedure

0.15 ml (1.4 mmol) of methyl acetoacetate in 2 ml of absolute tetrahydrofuran is added dropwise under nitrogen to a suspension of 54.6 mg (1.82 mmol) of 80% strength . sodium hydride in 5 ml of absolute tetrahydrofuran at -5° C. After 15 minutes, 0.89 ml (1.4 mmol) of 15% strength butyllithium in n-hexane is added dropwise at the same temperature and after a further 15 minutes 408 mg (1.8 mmol) of dry zinc bromide in 5 ml of absolute tetrahydrofuran are added. The mixture is allowed to stir for a further 15 minutes at -5° C., 400 mg (0.91 mmol) of the compound from Example 68 dissolved in 10 ml of dry tetrahydrofuran are added and the mixture is stirred overnight. Saturated ammonium chloride solution is added to the mixture and it is extracted several times using ether. The organic phase is dried over magnesium sulphate and concentrated in vacuo, and the residue is chromatographed on a column (silica gel 70-230 mesh, using ethyl acetate/petroleum ether 3:7).

Workup

  1. customat -5° C
  2. additionare added
  3. additionare added
  4. stirringthe mixture is stirred overnight
  5. extractionis extracted several times
  6. dry with materialThe organic phase is dried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. customthe residue is chromatographed on a column (silica gel 70-230 mesh, using ethyl acetate/petroleum ether 3:7)

Sources & evidence

ORD record
ord-d52381e39a8948b6a21513f5e0af145a
Source dataset
uspto-grants-1991_04
Patent number
US05006530

Reaction notes

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