Ethyl Acetoacetate → HCID 54116819, compound

HRID 330632Notes

Reaction equation

HRID 330632 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[Li]CCCC.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=[C:25]([C:30]2[N:34]([CH3:35])[N:33]=[N:32][N:31]=2)[CH:26]=[CH:27][CH:28]=[O:29])=[CH:20][CH:19]=1>O1CCCC1>[F:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=[C:25]([C:30]2[N:34]([CH3:35])[N:33]=[N:32][N:31]=2)[CH:26]=[CH:27][CH:28]([OH:29])[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 53904180HCID 53904180, compoundHCID 178418339Butyllithium

Product 1

HCID 54116819HCID 54116819, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a chilled suspension (0° C., ice-water bath) of NaH (0.64 g, 16.0 mmoles) (60% in mineral oil) in 20 mL Of dry tetrahydrofuran under argon was added ethyl acetoacetate 2.04 mL (16.0 mmoles) in 4 equal portions. The homogeneous clear solution was stirred at 0° C. for 30 minutes followed by the dropwise addition of 6.4 mL of 2.5 Molar n-BuLi (16.0 mmoles) over a period of 15 minutes. The orange dianion solution was stirred at 0° C. for an additional hour. The ice-water bath was replaced by an acetone-dry ice bath at -78° C. and the dianion was transferred via a cannula into a tetrahydrofuran (20 mL) solution containing 5,5-bis(4-fluorophenyl)-4-(1-methyl-1H-tetrazol-5-yl)-2,4-pentadienal (2.82 g, 8.01 mmoles). Analytical TLC showed the major desired product at Rf =0.15 (50% EtAOc in hexanes) and a minor product at Rf =0.2. The crude reaction mixture was diluted with 40 mL of 1N HCl and the aqueous layer was extracted with ethyl acetate (50 mL×2). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. The desired product was purified by flash silica gel column chromatography eluted with 20% EtOAc in hexanes (v/v) to give 2.26 g (58.5%) of the title compound. MS (CI): m/e=483 for (M+H)+.

Workup

  1. stirringThe orange dianion solution was stirred at 0° C. for an additional hour

Sources & evidence

ORD record
ord-c78f41d0ebab4bbf8e1d01487ec676a8
Source dataset
uspto-grants-1990_01
Patent number
US04897490

Reaction notes

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