Methyl acetoacetate → HCID 13826444, compound

HRID 1906928Notes

Reaction equation

HRID 1906928 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=2)[C:20]([CH2:28][CH2:29][CH:30]=[O:31])=[C:19]([CH3:32])[CH:18]=1>C1COCC1.CCCCCC>[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=2)[C:20]([CH2:28][CH2:29][CH:30]([OH:31])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:19]([CH3:32])[CH:18]=1

Participants

7

Reactant 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydride2×HCID 13826442HCID 13826442, compoundHCID 178418339Butyllithium

Product 1

HCID 13826444HCID 13826444, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Methyl acetoacetate (0.292 g, 2.64 mmoles) dissolved in dry THF (2 ml) is added dropwise via a syringe through a septum to a stirred suspension of sodium hydride (0.127 g of a 50% NaH in mineral oil, 2.64 mmoles) in dry THF (7 ml) which had been chilled in an ice-water bath. The reaction was stirred in the cold for 15 minutes at which time a clear solution was obtained. To this solution in the cold was added n-butyl lithium (1.80 ml of a 1.47M solution in hexane; 2.64 mmoles) via syringe through the septum dropwise in about 5 minutes. The orange solution is stirred with ice-water bath for 15 minutes and then cooled to -78° C. in a dry ice-acetone bath. To this cold stirred reaction was added dropwise via syringe, 3-(4,7-dichloro-2-methylnaphthalen-1-yl)propanal (0.6715 g, 2.513 mmoles) dissolved in dry THF (5 ml). The reaction is allowed to stir at -78° for 15 minutes, then allowed to warm to 0° by emersing the reaction flask in an ice-water bath. When ice separated from the flask, the reaction was worked up by partitioning it between ether (150 ml) and water containing 0.6 ml of 12N HCl. Extracted the water layer with ether. The combined ether extracts are washed with water twice then with saturated solution of NaHCO3. The ether was dried (MgSO4) and the solvent removed in vacuo to leave 0.96 g of crude title Rf =0.45 (silica, 5% acetone/CH2Cl2) which was used in the next step without further purification.

Workup

  1. temperaturehad been chilled in an ice-water bath
  2. customwas obtained
  3. wait2.64 mmoles) via syringe through the septum dropwise in about 5 minutes
  4. stirringThe orange solution is stirred with ice-water bath for 15 minutes
  5. stirringTo this cold stirred
  6. customreaction
  7. additionwas added dropwise via syringe
  8. stirringto stir at -78° for 15 minutes
  9. temperatureto warm to 0°
  10. customWhen ice separated from the flask
  11. customby partitioning it between ether (150 ml) and water containing 0.6 ml of 12N HCl
  12. extractionExtracted the water layer with ether
  13. washThe combined ether extracts are washed with water twice
  14. dry with materialThe ether was dried (MgSO4)
  15. customthe solvent removed in vacuo
  16. customto leave 0.96 g of crude title Rf =0.45 (silica, 5% acetone/CH2Cl2) which
  17. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-a44cabdf84b4423c89036648220c5904
Source dataset
uspto-grants-1987_03
Patent number
US04654363

Reaction notes

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