2-(2-iodoethoxy)oxane

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: 6.84 g of methyl 4-chloro-3-hydroxy-5-nitro-benzoate were dissolved in acetone (150 ml), treated at RT in succession with 10.19 g of potassium carbonate and 11.19 g of 2-(2-iodo-ethoxy)-tetrahydro-pyran and the mixture was heated at reflux for 16 hours. Subsequently, the mixture was poured into water, extracted with ethyl acetate, the organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was flash chromatographed on silica gel with hexane/ether (2/1) as the eluent. There was thus obtained the desired methyl 4-chloro-3-nitro-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate as as a pale yellow solid. the mixture was heated at reflux for 16 hours extracted with ethyl acetate the organic phase was dried over sodium sulphate concentrated on a rotary evaporator chromatographed on silica gel with hexane/ether (2/1) as the eluent

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

Procedure: Freshly distilled dihydropyran (Aldrich, 59.0-g, 0.7 mol) was added dropwise to a cooled solution of 2-iodoethanol (Aldrich, 98 g, 0.57 mol) in Et2O (1 L) containing 0.1 g of p-toluenesulfonic acid (Eastman). The solution was then stirred for 1 h at 5°. Solid K2CO3 (Mallinckrodt, 5 g) was then added to the reaction mixture and the resulting suspension stirred an additional 1 h at RT. The reaction was then filtered and the remaining solid washed with Et2O (1 L). The organic solutions were combined and concentrated rotary evaporation (in a flask washed with 1% NEt3 in H2O). The crude 2-(2-iodoethoxy)tetrahydro-2-H-pyran (~100 g, 68.9%) was used without further purification. the resulting suspension stirred an additional 1 h at RT The reaction was then filtered the remaining solid washed with Et2O (1 L) concentrated rotary evaporation (in a flask washed with 1% NEt3 in H2O) The crude 2-(2-iodoethoxy)tetrahydro-2-H-pyran (~100 g, 68.9%) was used without further purification

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

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

Procedure: The reaction was carried out in a manner similar to Reference Example 5 except for using 2.0 g (11.4 mmol) of methyl 2-indolecarboxylate, 0.55 g (13.7 mmol) of 60% sodium hydroxide, 3.63 g (13.7 mmol) of 2-(2-iodo-ethoxy)tetrahydropyran (prepared from 2-iodoethanol and 3,4-dihydro-2H-pyran) and 50 ml of dimethylformamide. Thus, 2.87 g (83.0%) of methyl 1-[2-(2-tetrahydro-pyranyl)oxyethyl]-2-indolecarboxylate was obtained.

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

Procedure: To a solution of 3-sulfino-benzoic acid (1 g) and 2-iodoethyl tetrahydro-2H-pyran-2-yl ether (1.4 g) in water (20 ml) and ethanol (20 ml) was added NaOH solution to give a pH of 9. The resulting mixture was refluxed for 3 hours before evaporation of the ethanol. The aqueous was acidified to pH3 and the product extracted with EtOAc. The organic layer was separated, dried with MgSO4 and solvent removed by evaporation to give the sub-title compound (0.25 g). to give a pH of 9 the product extracted with EtOAc The organic layer was separated dried with MgSO4 and solvent removed by evaporation

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

Procedure: To a solution of 3-sulfino-benzoic acid (1 g) and 2-iodoethyl tetrahydro-2H-pyran-2-yl ether (1.4 g) in water (20 ml) and ethanol (20 ml) was added NaOH solution to give a pH of 9. The resulting mixture was refluxed for 3 hours before evaporation of the ethanol. The aqueous was acidified to pH3 and the product extracted with EtOAc. The organic layer was separated, dried with MgSO4 and solvent removed by evaporation to give the sub-title compound (0.25 g). to give a pH of 9 the product extracted with EtOAc The organic layer was separated dried with MgSO4 and solvent removed by evaporation

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

Procedure: The reaction was carried out in a manner similar to Reference Example 5 except for using 2.0 g (11.4 mmol) of methyl 2-indolecarboxylate, 0.55 g (13.7 mmol) of 60% sodium hydroxide, 3.63 g (13.7 mmol) of 2-(2-iodo-ethoxy)tetrahydropyran (prepared from 2-iodoethanol and 3,4-dihydro-2H-pyran) and 50 ml of dimethylformamide. Thus, 2.87 g (83.0%) of methyl 1-[2-(2-tetrahydro-pyranyl)oxyethyl]-2-indolecarboxylate was obtained.

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

Procedure: The reaction was carried out in a manner similar to Reference Example 5 except for using 2.0 g (11.4 mmol) of methyl 2-indolecarboxylate, 0.55 g (13.7 mmol) of 60% sodium hydroxide, 3.63 g (13.7 mmol) of 2-(2-iodo-ethoxy)tetrahydropyran (prepared from 2-iodoethanol and 3,4-dihydro-2H-pyran) and 50 ml of dimethylformamide. Thus, 2.87 g (83.0%) of methyl 1-[2-(2-tetrahydro-pyranyl)oxyethyl]-2-indolecarboxylate was obtained.

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

Procedure: 6.84 g of methyl 4-chloro-3-hydroxy-5-nitro-benzoate were dissolved in acetone (150 ml), treated at RT in succession with 10.19 g of potassium carbonate and 11.19 g of 2-(2-iodo-ethoxy)-tetrahydro-pyran and the mixture was heated at reflux for 16 hours. Subsequently, the mixture was poured into water, extracted with ethyl acetate, the organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was flash chromatographed on silica gel with hexane/ether (2/1) as the eluent. There was thus obtained the desired methyl 4-chloro-3-nitro-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate as as a pale yellow solid. the mixture was heated at reflux for 16 hours extracted with ethyl acetate the organic phase was dried over sodium sulphate concentrated on a rotary evaporator chromatographed on silica gel with hexane/ether (2/1) as the eluent

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

Procedure: 6.84 g of methyl 4-chloro-3-hydroxy-5-nitro-benzoate were dissolved in acetone (150 ml), treated at RT in succession with 10.19 g of potassium carbonate and 11.19 g of 2-(2-iodo-ethoxy)-tetrahydro-pyran and the mixture was heated at reflux for 16 hours. Subsequently, the mixture was poured into water, extracted with ethyl acetate, the organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was flash chromatographed on silica gel with hexane/ether (2/1) as the eluent. There was thus obtained the desired methyl 4-chloro-3-nitro-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate as as a pale yellow solid. the mixture was heated at reflux for 16 hours extracted with ethyl acetate the organic phase was dried over sodium sulphate concentrated on a rotary evaporator chromatographed on silica gel with hexane/ether (2/1) as the eluent