6-phenylhexanoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-amino-3-cyanopyridine [24517-64-4] (200 mg, 1.7 mmol) in CH2Cl2 (3 ml) and pyridine (3 ml) was added a solution of 6-phenylhexanoic acid chloride (1.5 eq) in CH2Cl2 (1 ml) and the reaction mixture was stirred overnight at ambient temperature. Water was added, the phases were separated and the pH of the inorganic layer was adjusted (pH 7). The inorganic phase was extracted with EtOAc (3 times), the combined organic layers were washed with brine, dried over Na2SO4, filtrated and concentrated in vacuo. Trituration from diethyl ether yielded 6-phenyl-hexanoic acid (3-cyano-pyridin-2-yl)-amide 360 mg (73%) as a white solid, MS (m/e): 294.3 [M+H+]. the phases were separated The inorganic phase was extracted with EtOAc (3 times) the combined organic layers were washed with brine dried over Na2SO4 filtrated concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 6-phenylhexanoic acid [5581-75-9] (1.45 g, 7.6 mmol) in CH2Cl2 (15 ml) was treated with oxalyl chloride (0.72 ml, 8.6 mmol) in the presence of a catalytic amount of DMF. The solution was stirred for 2 h at ambient temperature. The solvent was evaporated to give crude 6-phenylhexanoic acid chloride, which was used without further purification in the next step. The solvent was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 65.7 Grams of 6-phenylhexanoyl chloride was added by drops to a mixture of 19.2 g of propargyl alcohol, 34.7 g of triethylamine and 500 ml of dry toluene with stirring and ice-cooling. After dropwise addition, the resultant solution was stirred for additional 12 hours at room temperature. The thus stirred solution was poured into ice water. The toluene layer was separated from the resulting mixture. The aqueous layer was extracted once with toluene. These toluene layers were combined, washed with water and then with an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off from the dried layer under reduced pressure. The resulting residue was distilled under reduced pressure to obtain 157.9 g of propargyl 6-phenylhexanoate. ice-cooling After dropwise addition The toluene layer was separated from the resulting mixture The aqueous layer was extracted once with toluene washed with water with an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate The solvent was distilled off from the dried layer under reduced pressure The resulting residue was distilled under reduced pressure

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (4-benzylthio-2-oxoazetidin-1-yl)acetamide (0.63 g, 2.52 mmol) in dry THF (15 ml) was added to a suspension of sodium hyride (60% in oil, 0.10 g, 2.5 mmol) in dry THF at -10° C. under a nitrogen atmosphere. The reaction was stirred at -10° C. for 10 minutes and was then treated with a solution of 6-phenylhexanoyl chloride (0.58 g, 2.75 mmol) in dry THF (5 ml) dropwise over 2 minutes maintaining the temperature at -10° C. The cooling bath was removed an after stirring for 60 minutes the reaction was treated with sodium hydride (50 mg, 1.25 mmol) and 6-phenylhexanoyl chloride (0.29 g, 1.38 mmol) in dry THF (2 ml). The reaction was stirred for 60 minutes, poured into ice/brine (100 ml), extracted with ethyl acetate (2×50 ml). The organic extracts were combined, washed with aq. sat. NaHCO3 solution, brine, dried (MgSO4) and evaporated under reduced pressure to an orange oil. Purification by repeated column chromatography eluted with hexane:ethyl acetate (3:1 to 1:1) gave the product as a colourless oil (0.22 g, 21% yield, contains 10% 6-phenylhexanoic acid) 1H nmr δ (CDCl3) 1.3-1.7 (6H, m, 3×CH2), 2.44 (2H, t, J=7.4 Hz, NHCOCH2), 2.62 (2H, t, J=7.6 Hz, PhCH2), 2.96, 3.02 (1H, dd, J=2.4, 15.3 Hz, H3), 3.39, 3.45 (1H, dd, J=5.1, 15.3 Hz, H3), 3.61, 4.32 (each 1H, d, J=18.8 Hz, NCH2CO), 3.76 (2H, m, SCH2), 4.9 (1H, m, H4), 7.1-7.3 (10H, m, 2×Ph--H), 8.17 (1H, m, NH) maintaining the temperature at -10° C The cooling bath was removed an after stirring for 60 minutes the reaction The reaction was stirred for 60 minutes extracted with ethyl acetate (2×50 ml) washed with aq. sat. NaHCO3 solution, brine dried (MgSO4) evaporated under reduced pressure to an orange oil Purification eluted with hexane:ethyl acetate (3:1 to 1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Phenylhexanoic acid (2.5 g, 13 mmol) was treated with thionyl chloride (3.0 ml, 41.1 mmol) and stirred under reflux for 3 h. The mixture was evaporated under reduced pressure to remove thionyl chloride and then distilled at 92-95° C./0.1 mbar to give the product as a colourless oil (2.57 g, 94%). under reflux for 3 h The mixture was evaporated under reduced pressure to remove thionyl chloride distilled at 92-95° C./0.1 mbar