1-Butanone, 1-cyclohexyl-4,4-diethoxy-2-phenyl- synthesis

Yield:1347677-19-3 42%

Reaction Conditions:

Stage #1: 1-cyclohexyl-2-phenylethanonewith sodium hydride in DMF (N,N-dimethyl-formamide) at 20; for 1 h;
Stage #2: Bromoacetaldehyde diethyl acetal in DMF (N,N-dimethyl-formamide) at 20 - 80; for 2 h;

Steps:

5 Example 5 (Comparative); 1- [[ (RS, SR)-4-CYCLOHEXYL-4-HYDROXY-3-PHENYL-BUTYL]-4- (2-METHOXYPHENYL)-PIPERAZINE]; 4-Cyclohexyl-4-oxo-3-phenyl-butyraldehyde diethyl acetal (Compound 5b)

To a solution of 1.78 g of Compound 5a in 30 ml of anhydrous dimethylformamide were added at r. t. 0.37 g of 60% sodium hydride oil dispersion and the mixture was stirred at r. t. for 1 h. 1.46 ml of 2-bromoacetaldeide diethyl acetal was added and the mixture stirred at r. t. for 1 h and at [80°C] for 1 h, cooled to r. t. , quenched with water and extracted with EtOAc. The collected organic layers were washed with water, dried [(NA2SO4)] and the solvent was evaporated under vacuum. The crude was purified by flash chromatography eluting with petroleum ether-EtOAc 95: 5 to give 1.17 g (42%) of the title compound. 'H-NMR (200 [MHZ,] [CDC13,] [6)] : 1.01-1. 98 (m, 17H), 2.28-2. 48 [(M,] 2H), 3.30-3. 71 (m, 4H), 3.98 [. (T,] 1H), 4.25 (t, 1H), 7.12-7. 39 [(M,] 5H)

References:

WO2003/106444,2003,A1 Location in patent:Page 32