2-(4-iodophenyl)acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-[4-(cyanomethyl)phenyl]-(1S,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide was prepared as described above for the preparation of the N-[4-(cyanomethyl)phenyl]-(1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide isomer, i.e., by coupling the (1S,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide prepared in steps A to C above with 4-(cyanomethyl)phenyl iodide. The (1S,2S,5R)-material (neoisomer) has the following properties with structure confirmed by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate. by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet was charged with 10.00 g (0.0546 mol) of (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide, 0.522 g (0.0027 mol) copper (I) iodide, 13.26 g (0.0546 mol) of 4-(cyanomethyl)phenyl iodide, 23.18 g (0.109 mol) of potassium phosphate. The system was purged with nitrogen and a magnetic stir bar was added. After the addition of 170 mL of toluene, 3.42 g (0.190 mol) of water and 0.964 g (0.0109 mol) of N,N′-dimethylethylene diamine, the mixture was heated to 100° C. and stirred for 21 h under nitrogen. The crude reaction mixture was filtered through 50 g of silica gel (wet with 1:1 ethyl acetate/methylene chloride), and the bed was rinsed three times with 1:1 ethyl acetate/methylene chloride (150+75+75 mL). Concentration of the mixture in vacuo provided N-[4-(cyanomethyl)phenyl]-(1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide as a thick oil oil which was further purified by flash chromatography on silica gel eluting with mixtures of ethyl acetate and hexanes. The product has the following properties with the structure confirmed by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate. A 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet The system was purged with nitrogen and a magnetic stir bar was added The crude reaction mixture was filtered through 50 g of silica gel (wet with 1:1 ethyl acetate/methylene chloride) the bed was rinsed three times with 1:1 ethyl acetate/methylene chloride (150+75+75 mL)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the above 4-bromothiophen-2-ylmethanol (4.83 g, 25 mmol) and 63 ml of 47% hydrobromic acid was stirred vigorously for 30 minutes at room temperature. The reaction mixture was extracted with pentane to give 5.31 g (yield: 82.8%) of 2-bromomethyl-4-bromothiophene as a pale yellow oil. Thus obtained 5.12 g of 2-bromomethyl-4-bromothiophene was reacted with sodium cyanide according to the same procedure as in the synthesis of 4-iodophenylacetonitrile of example 5 to give 1.50 g (yield: 37.0%)of 4-bromothiophen-2-ylacetonitrile as a white crystal, removing by-product of α,α-bis[(4-bromothiophen-2-yl)methyl]-4-bromothiopheneaetonitrile by means of recrystalization.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a hot solution (50° C.) of sodium cyanide 0.49 g, 10.0 mmom, purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) was added the above 4-iodobenzyl bromide (1.48 g, 5.0 mmol) and the mixture was stirred for three hours at ambient temperature. To the resultant reaction mass was added water and extracted with hexane. The solvent was removed to give 0.84 g (yield: 69%) of 4-iodophenylacetonitrile as a white crystalline. To the resultant reaction mass extracted with hexane The solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-bromomethylbenzonitrile (white crystal), 2.0 g (yield: 51.0%), were obtained according to the same method as that of synthesis of 4-iodophenylacetonitrile of Example 5 except that 2.34 g (20 mmole) of p-tolunitrile (purchased from Tokyo Kasei) were used. Subsequently, 438 mg (yield: 34.2%) of light yellow crystals of 4-cyanophenylacetonitrile were obtained according to the same method as that of synthesis of 4-iodophenylacetonitrile of Example 5 except that 1.76 g (9.0 mmole) of the above 4-bromomethylbenzonitrile were used and that purification was performed according to silica gel column chromatography and recrystallization.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the above 4-bromothiophen-2-ylmethanol (4.83 g, 25 mmol) and 63 ml of 47% hydrobromic acid was stirred vigorously for 30 minutes at room temperature. The reaction mixture was extracted with pentane to give 5.31 g (yiel: 82.8%) of 2-bromomethyl-4-bromothiophene as a pale yellow oil. Thus obtained 5.12 g of 2-bromomethyl-4-bromothiophene was reacted with sodium cyanide according to the same procedure as in the synthesis of 4-iodophenylacetonitrile of example 5 to give 1.50 g (yield: 37.0%) of 4-bromothiophen-2-ylacetonitrile as a white crystal, removing by-product of α,α-bis[(4-bromothiophen-2-yl)methyl]-4-bromothiopheneaetonitrile by means of recrystalization.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the above 4-bromothiophen-2-ylmethanol (4.83 g, 25 mmol) and 63 ml of 47% hydrobromic acid was stirred vigorously for 30 minutes at room temperature. The reaction mixture was extracted with pentane to give 5.31 g (yiel: 82.8%) of 2-bromomethyl-4-bromothiophene as a pale yellow oil. Thus obtained 5.12 g of 2-bromomethyl-4-bromothiophene was reacted with sodium cyanide according to the same procedure as in the synthesis of 4-iodophenylacetonitrile of example 5 to give 1.50 g (yield: 37.0%) of 4-bromothiophen-2-ylacetonitrile as a white crystal, removing by-product of α,α-bis[(4-bromothiophen-2-yl)methyl]-4-bromothiopheneaetonitrile by means of recrystalization.