2-Phenylacetophenone → HCID 19101430, compound

HRID 1975256Notes

Reaction equation

HRID 1975256 reaction equation
C(NC(C)C)(C)C.[Li].[CH3:9][N:10]([CH3:14])[C:11](=[O:13])[CH3:12].[CH2:15]([C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH3:9][N:10]([CH3:14])[C:11](=[O:13])[CH2:12][C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([OH:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 99482-PhenylacetophenoneHCID 31374Dimethylacetamide2×HCID 45051747Lithium diisopropylamine

Product 1

HCID 19101430HCID 19101430, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred ice-cold (0° C.) solution of 10 g (0.1 mole) diisopropylamine in 100 ml of anhydrous THF under nitrogen gas is added, dropwise, 40 ml (2.5 M) n-butyllithium over a period of about 15 min to form lithium diisopropylamine solution, which is a pale yellow. To the amine solution is added 8.8 g (0.1 mole) N,N-dimethylacetamide in 10 ml THF, dropwise, via syringe, over a period of 10 min. The resulting lithium enolate of N,N-dimethylacetamide solution is deep yellow, and is stirred for 45 min at 0° C. A solution of 18.5 g (0.095 mole) benzylphenylketone in 20 ml of THF is added rapidly over a period of about 2 min to the enolate solution. An orange N,N-dimethyl-3,4-diphenyl-3-hyroxybutyramide solution is formed, and is stirred at 0° C. for about 15 min. Then 40 ml (2.5 M) n-butyllithium is added dropwise via syringe to form a deep red dianion solution. The dianion solution is stirred at about -20° C. for 30 min. Methyl bromide (19 g, 0.2 mole, 2 equivalents) in 20 ml THF is added slowly to methylate the dianion. The resulting N,N-dimethyl-2-methyl-3,4-diphenyl-3-hydroxybutyramide mixture is held at about -20° C. for about 1 h, and a cloudy yellow suspension is formed. The suspension is warmed to room temperature (25° C.), then quenched with 200 ml of a 0° C. solution of 2 N HCl, which is added with rapid stirring. The quenched, pale yellow solution is diluted with 200 ml ether. The organic layer is recovered and washed with brine and dried over anhydrous MgSO4. The mixture is filtered, yielding a pale yellow solution of N,N-dimethyl-2-methyl-3,4-diphenyl-3-hydroxybutyramide, which is reduced in the following step.

Sources & evidence

ORD record
ord-f3e7a1f67ec24ac08dbdec924f3eadff
Source dataset
uspto-grants-1994_02
Patent number
US05284975

Reaction notes

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