Ethyl Acetoacetate → HCID 53655424, compound

HRID 1195340Notes

Reaction equation

HRID 1195340 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[Li]CCCC.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[C:25]([C:30]2[N:31]=[N:32][N:33]([C:35]([CH3:38])([CH3:37])[CH3:36])[N:34]=2)[CH:26]=[CH:27][CH:28]=[O:29])=[CH:20][CH:19]=1>O1CCCC1>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[C:25]([C:30]2[N:31]=[N:32][N:33]([C:35]([CH3:38])([CH3:36])[CH3:37])[N:34]=2)[CH:26]=[CH:27][CH:28]([OH:29])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 54233395HCID 54233395, compoundHCID 178418339Butyllithium

Product 1

HCID 53655424HCID 53655424, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of the dianion of ethyl acetoacetate (400 μL, 3.1 mmoles) in 8 mL of dry tetrahydrofuran was generated as described in Example 10 using 130 mg (3.2 mmoles) of NaH (60% in mineral oil) and 2.5M n-BuLi in hexanes (1.27 mL, 3.2 mmoles) at 0° C. under argon. The orange dianion solution, after being chilled to -78° C., was transferred via a cannula into a tetrahydrofuran (12 mL) solution at -78° C. containing 5,5-bis(4-fluorophenyl)-4-[2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]-2,4-pentadienal (0.96 g, 2.4 mmoles). The reaction mixture was stirred at -78° C. for five minutes. Analytical TLC eluted once with 50% (v/v) EtOAc in hexanes showed the major product spot at Rf =0.35. The reaction mixture was diluted with 20 mL of 1N HCl and the organic material was extracted with EtOAc (20 mL×2). The organic layers were combined, dried over MgSO4, evaporated under reduced pressure, and dried under high vacuum (0.001 mmHg) at ambient temperature overnight (16 hours) to give the title compound which was used in the next step without further purification.

Workup

  1. washAnalytical TLC eluted once with 50% (v/v) EtOAc in hexanes
  2. additionThe reaction mixture was diluted with 20 mL of 1N HCl
  3. extractionthe organic material was extracted with EtOAc (20 mL×2)
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customdried under high vacuum (0.001 mmHg) at ambient temperature overnight (16 hours)

Sources & evidence

ORD record
ord-75fb38e85ef14c2b9e6805d83e7ed3b2
Source dataset
uspto-grants-1992_05
Patent number
US05110940

Reaction notes

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