3-IODOPHENYLACETONITRILE

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 3-iodophenylacetonitrile (2.43 g, 10 mmol), bis-(2-chloroethyl)ether (1.57 g, 11 mmol), hexadecyltributylphosphonium bromide (250 mg, 0.5 mmol) and 50% aqueous sodium hydroxide (20 ml) was stirred vigorously for 1 h at room temperature. The mixture was neutralized with 6 N aqueous HCl, transferred to a separatory funnel and extracted with ethyl acetate (50 ml×3). The combined extracts were washed with 2 N aqueous HCl (50 ml), water (50 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo. The residual crude solids were collected and washed with cold Et2O (30 ml) to afford 2.38 g (76%) of the titled compound as white solids. transferred to a separatory funnel extracted with ethyl acetate (50 ml×3) The combined extracts were washed with 2 N aqueous HCl (50 ml), water (50 ml) and brine (50 ml) dried (MgSO4) concentrated in vacuo The residual crude solids were collected washed with cold Et2O (30 ml)

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

Procedure: A mixture of 3-iodophenylacetonitrile (2.43 g, 10 mmol), bis-(2-chloroethyl)ether (1.57 g, 11 mmol), hexadecyltributylphosphonium bromide (250 mg, 0.5 mmol) and 50% aqueous sodium hydroxide (20 ml) was stirred vigorously for 1 h at room temperature. The mixture was neutralized with 6 N aqueous HCl, transferred to a separatory funnel and extracted with ethyl acetate (50 ml×3). The combined extracts were washed with 2 N aqueous HCl (50 ml), water (50 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo. The residual crude solids were collected and washed with cold Et2O (30 ml) to afford 2.38 g (76%) of the titled compound as white solids. transferred to a separatory funnel extracted with ethyl acetate (50 ml×3) The combined extracts were washed with 2 N aqueous HCl (50 ml), water (50 ml) and brine (50 ml) dried (MgSO4) concentrated in vacuo The residual crude solids were collected washed with cold Et2O (30 ml)

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

Procedure: The titled compounds were prepared according to the procedure described in Example 25A except that 3-iodophenyacetonitrile and 1-iodo-2-(2-iodoethoxy)propane were used in place of 3,5-difluorophenylacetonitrile and bis-(2-chloroethyl)ether. The diastereomers were separated by silica gel column chromatography to afford 1.46 g (38%) of a less polar isomer, (2SR, 4RS)-4-cyano-4-(3-iodophenyl)-2-methyl-3,4,5,6-tetrahydro-2H-pyran; and 1.31 g (34%) of a more polar isomer, (2SR, 4SR)-4-cyano-4-(3-iodophenyl)-2-methyl-3,4,5,6-tetrahydro-2H-pyran. The diastereomers were separated by silica gel column chromatography

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

Procedure: 2-(4-Chlorophenyl)-2-(4-nitrophenyl)-1,3-dioxolane (38.7 g, 127 mMol) was suspended in 190 mL of methanol (MeOH) under an atmosphere of dry N2. To this solution was added (3-iodophenyl)acetonitrile (46.3 g, 190 mMol) and 25.4 g (625 mMol) of sodium hydroxide (NaOH). The solution was then heated to reflux and reacted at this temperature for 2 hours. The reaction mixture was cooled to ambient temperature and the MeOH was removed under vacuum. The resulting red oil was partitioned between dichloromethane (DCM) and 0.1 N aqueous NaOH. The DCM layer was washed successively with 0.1 N aqueous NaOH and then brine. The DCM layer was dried over MgSO4, filtered and concentrated under vacuum to give a dark red oil. The oil was stirred in MeOH and the titled compound precipitated out as a yellow solid. The yellow solid was washed with MeOH and dried under vacuum to give 52.4 g of the titled compound which was used without further purification. The solution was then heated to reflux reacted at this temperature for 2 hours the MeOH was removed under vacuum The resulting red oil was partitioned between dichloromethane (DCM) and 0.1 N aqueous NaOH The DCM layer was washed successively with 0.1 N aqueous NaOH The DCM layer was dried over MgSO4 filtered concentrated under vacuum to give a dark red oil the titled compound precipitated out as a yellow solid The yellow solid was washed with MeOH dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of potassium cyanide (4 g) and tetra-n-butylammonium bromide (0.32 g) in water (20 ml) was added to a solution of 3-iodobenzyl bromide (5.92 g) in methylene chloride (20 ml) and the mixture was heated to reflux for 2 hours. The organic phase was separated, washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using methylene chloride as eluent to give 3-iodophenylacetonitrile (4.4 g). the mixture was heated to reflux for 2 hours The organic phase was separated washed with water dried (MgSO4) evaporated The residue was purified by column chromatography

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

Procedure: A mixture of potassium cyanide (4 g) and tetra-n-butylammonium bromide (0.32 g) in water (20 ml) was added to a solution of 3-iodobenzyl bromide (5.92 g) in methylene chloride (20 ml) and the mixture was heated to reflux for 2 hours. The organic phase was separated, washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using methylene chloride as eluent to give 3-iodophenylacetonitrile (4.4 g). the mixture was heated to reflux for 2 hours The organic phase was separated washed with water dried (MgSO4) evaporated The residue was purified by column chromatography

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

Procedure: A mixture of potassium cyanide (4 g) and tetra-n-butylammonium bromide (0.32 g) in water (20 ml) was added to a solution of 3-iodobenzyl bromide (5.92 g) in methylene chloride (20 ml) and the mixture was heated to reflux for 2 hours. The organic phase was separated, washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using methylene chloride as eluent to give 3-iodophenylacetonitrile (4.4 g). the mixture was heated to reflux for 2 hours The organic phase was separated washed with water dried (MgSO4) evaporated The residue was purified by column chromatography