Ethyl Acetoacetate → HCID 86744243, compound

HRID 1087743Notes

Reaction equation

HRID 1087743 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.[CH:17]([C:20]1[N:24]2[N:25]=[CH:26][C:27]3[C:32]([C:23]2=[C:22]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:21]=1/[CH:39]=[CH:40]/[CH:41]=[O:42])=[CH:31][CH:30]=[CH:29][CH:28]=3)([CH3:19])[CH3:18]>O1CCCC1.CCCCCC>[OH:42][CH:41](/[CH:40]=[CH:39]/[C:21]1[C:22]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[N:25][N:24]2[C:20]=1[CH:17]([CH3:19])[CH3:18])[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8]

Participants

7

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 22163770HCID 22163770, compoundHCID 178418339Butyllithium

Product 1

HCID 86744243HCID 86744243, compoundYield 42.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-10 °C

Procedure

A stirred suspension of sodium hydride (80% dispersion in oil, 112 mg; 3.7 mmol) in dry tetrahydrofuran (15 ml) was treated with ethyl acetoacetate (0.43 g) under an atmosphere of argon, maintaining the temperature at -10° C. The mixture was stirred for 30 minutes and then it was treated with a solution of butyl lithium in hexane (2.5M; 1.38 ml), still maintaining the temperature at -10° C. The mixture was stirred for a further period of 20 minutes and then it was treated dropwise with a solution of (E)-3-(3-isopropyl-1-phenylpyrrolo[2,1-a]phthalazin-2-yl)propenal (0.56 g) in tetrahydrofuran (5 ml) at -10° C., and the resulting mixture was stirred at -10° C. for 1 hour. The reaction mixture was then quenched at -10° C. by treatment with saturated aqueous ammonium chloride solution (15 ml). The mixture was allowed to warm to the ambient temperature and then it was partitioned between water (20 ml) and diethyl ether (50 ml). The organic layer was separated and the aqueous layer was extracted with diethyl ether (50 ml). The combined organic layers were dried over magnesium sulphate, evaporated and subjected to flash chromatography on silica gel, using as eluant a mixture of petroleum ether (b.p. 40°-60° C.) and diethyl ether (3:1 v/v), to give ethyl (E)-5-hydroxy-7-(3-isopropyl-1-phenylpyrrolo[2,1-a]phthalazin-2-yl)-3-oxohept-6-enoate (0.33 g) in the form of an orange oil. [NMR (in a mixture of CDCl3 and D2O): 1.27 (3H, t, J=7 Hz), 1.54 (6H, d, J=7 Hz), 2.52-2.62 (2H, m), 3.44 (2H, s), 3.78 (1H, septet, J=7 Hz), 4.21 (2H, q, J= 7 Hz), 4.50-4.62 (1H, m), 5.3 (1H, dd, J=16 Hz, 7 Hz), 6.65 (1H, dd, J=16 Hz, 1 Hz), 7.22-7.62 (9H, m), 8.24 (1H, s)].

Workup

  1. temperaturestill maintaining the temperature at -10° C
  2. stirringThe mixture was stirred for a further period of 20 minutes
  3. stirringthe resulting mixture was stirred at -10° C. for 1 hour
  4. customThe reaction mixture was then quenched at -10° C. by treatment with saturated aqueous ammonium chloride solution (15 ml)
  5. temperatureto warm to the ambient temperature
  6. customit was partitioned between water (20 ml) and diethyl ether (50 ml)
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with diethyl ether (50 ml)
  9. dry with materialThe combined organic layers were dried over magnesium sulphate
  10. customevaporated
  11. additiona mixture of petroleum ether (b.p. 40°-60° C.) and diethyl ether (3:1 v/v)

Sources & evidence

ORD record
ord-abcb673c5dfd48d5ad8377ebab57e784
Source dataset
uspto-grants-1990_10
Patent number
US04960775

Reaction notes

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