4-hydroxy-N,N-diphenyl-(4R)-2-Pentynamide Chemical Properties

Boiling point:

411.9±47.0 °C(Predicted)

Density 

1?+-.0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

13.24±0.20(Predicted)

Appearance

White to off-white Solid

4-hydroxy-N,N-diphenyl-(4R)-2-Pentynamide Usage And Synthesis

Application

4-hydroxy-N,N-diphenyl-(4R)-2-Pentynamide can be used as an organic synthesis intermediate and a pharmaceutical intermediate, mainly in laboratory research and development and chemical production processes.

Synthesis

Example 1 - Preparation of Amide Method A (R): this method is suitable for racemic or enantiomerically pure starting material butyn-2-ol. To a stirred solution of concentrated sulfuric acid (40 μL) in THF (240 mL) was sequentially added (R)-3-butyn-2-ol (40 g, 0.57 mol) followed by hexamethyldisilazane (49.6 g, 0.31 mol). The reaction was carried out at room temperature. The reaction solution was refluxed for 3-4 hours and then slowly cooled to -40°C. The resulting mixture was slowly added to hexyl lithium (2.5 M hexane solution, 249 mL, 0.62 mol) while keeping the reaction temperature at -40 °C. The above solution was mixed with a solution of diphenylcarbamoylimidazole (180 g, 0.68 mol) in a solvent mixture of THF (1088 mL) and toluene (435 mL) by means of a cooled static mixer using a pump and quenched directly to 5N sulfuric acid (560 mL, -50 °C). The quenched solution was slowly warmed to 25 °C and stirred for 1 hour. The organic layer was separated and washed twice sequentially with 5N sulfuric acid (80 mL) and 10% brine (200 mL each). The pH of the final brine wash solution was adjusted to 5-7 with 5% NaHCO3 solution. the organic layer was subsequently distilled and the solvent replaced with toluene (440 mL). The toluene solution was added to heptane (400 mL) at 85°C and filtered after slow cooling to 20°C. The filter cake was washed with a mixture of toluene (80 mL) and heptane (50 mL). Finally, the filter cake was dried in a vacuum oven at 50 °C to afford (R)-4-hydroxy-N,N-diphenyl-2-pentynamide in 84% yield (120.6 g, 99% purity). Melting point 105 °C. 1H NMR (400 MHz, DMSO-d6) δ 1.04 (d, J=6.4 Hz, 3H), δ 4.27 (dq, J=5.6 Hz, 6.4 Hz, 1H), δ 5.49 (d, J=5.6 Hz, 1H), δ 7.2-7.5 (m, 10H); 13C NMR (DMSO-d6) δ 23.7,56.3,76.9,96.4,126.8,127.0,128.5,129.2,129.4,129.6,141.5,142.2,152.9.

References

[1] Patent: WO2006/76452, 2006, A2. Location in patent: Page/Page column 27; 28
[2] Patent: WO2006/76415, 2006, A2. Location in patent: Page/Page column 37-38

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