4-chloro-1,1-dimethoxybutane

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

Procedure: A solution of ethyl-p-hydrazinobenzoate hydrochloride (10 g, 46 mmol) and 4-chlorobutanal dimethyl acetal (7.8 g, 46 mmol) in ethanol/water (5:1, 500 ml) was heated at reflux for 2 h. The solvent was removed under vacuum and the residue chromatographed through silica-gel eluting with dichloromethane/ethanol/ammonia (40:8:1) to give the title-indole as an oil (3.69 g). The hydrogen maleate salt was prepared, mp 127° C.; (Found: C, 59.46; H, 5.96; N, 8.47. C13H16N2O2.C4H4O4 requires C, 59.68; H, 5.93; N, 8.54%), m/e 232 (M+), δ(360 MHz, D2O) 1.43 (3H, t, J=7.1 Hz, Me); 3.21 (2H, t, J=7.0 Hz, CH2); 3.37 (2H, t, J=7.0 Hz, CH2); 4.42 (2H, q, J=7.1 Hz, CH2); 6.23 (2H, s, maleate-H); 7.40 (1H, s, indole-H); 7.56 (1H, d, J=8.8 Hz, aromatic-H); 7.88 (1H, dd, J=1.6 and 8.8 Hz, aromatic-H); 8.38 (1H, d, J=1.6 Hz, aromatic-H). at reflux for 2 h The solvent was removed under vacuum the residue chromatographed through silica-gel eluting with dichloromethane/ethanol/ammonia (40:8:1)

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

Procedure: A mixture of azetidine (2.0 g, 35.0 mmol), 4-chlorobutanal dimethylacetal (5.88 g, 39.0 mmol) and K2CO3 (5.38 g, 39.0 mmol), in anhydrous DMF (100ml), was stirred at room temperature for 72 h. Water (50 ml) was added and the mixture extracted with EtOAc (3×150 ml). The combined extracts were washed with H2O (3×50ml), dried (Na2SO4) and evaporated. The crude product was purified by distillation (1.2 g). δ (360 MHz, CDCl3) 1.35-1.42 (2H, m, CH2), 1.57-1.64 (2H, m, CH2), 2.00-2.40 (2H, m, CH2), 2.36 (2H, t, J=9.0 Hz, CH2), 3.15 (4H, m, t, J=7.0 Hz, 2 of CH2), 3.33 (6H, s, 2 of OMe), 4.35 (1H, t, J=5.7 Hz, CH). the mixture extracted with EtOAc (3×150 ml) The combined extracts were washed with H2O (3×50ml) dried (Na2SO4) evaporated The crude product was purified by distillation (1.2 g)

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

Procedure: A mixture of azetidine (2.0 g, 35.0 mmol), 4-chlorobutanal dimethylacetal (5.88 g, 39.0 mmol) and K2CO3 (5.38 g, 39.0 mmol), in anhydrous DMF (100ml), was stirred at room temperature for 72 h. Water (50 ml) was added and the mixture extracted with EtOAc (3×150 ml). The combined extracts were washed with H2O (3×50ml), dried (Na2SO4) and evaporated. The crude product was purified by distillation (1.2 g). δ (360 MHz, CDCl3) 1.35-1.42 (2H, m, CH2), 1.57-1.64 (2H, m, CH2), 2.00-2.40 (2H, m, CH2), 2.36 (2H, t, J=9.0 Hz, CH2), 3.15 (4H, m, t, J=7.0 Hz, 2 of CH2), 3.33 (6H, s, 2 of OMe), 4.35 (1H, t, J=5.7 Hz, CH). the mixture extracted with EtOAc (3×150 ml) The combined extracts were washed with H2O (3×50ml) dried (Na2SO4) evaporated The crude product was purified by distillation (1.2 g)

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

Procedure: A solution of ethyl-p-hydrazinobenzoate hydrochloride (10 g, 46 mmol) and 4-chlorobutanal dimethyl acetal (7.8 g, 46 mmol) in ethanol/water (5:1, 500 ml) was heated at reflux for 2 h. The solvent was removed under vacuum and the residue chromatographed through silica-gel eluting with dichloromethane/ethanol/ammonia (40:8:1) to give the title-indole as an oil (3.69 g). The hydrogen maleate salt was prepared, mp 127° C.; (Found: C, 59.46; H, 5.96; N, 8.47. C13H16N2O2.C4H4O4 requires C, 59.68; H, 5.93; N, 8.54%), m/e 232 (M+), δ(360 MHz, D2O) 1.43 (3H, t, J=7.1 Hz, Me); 3.21 (2H, t, J=7.0 Hz, CH2); 3.37 (2H, t, J=7.0 Hz, CH2); 4.42 (2H, q, J=7.1 Hz, CH2); 6.23 (2H, s, maleate-H); 7.40 (1H, s, indole-H); 7.56 (1H, d, J=8.8 Hz, aromatic-H); 7.88 (1H, dd, J=1.6 and 8.8 Hz, aromatic-H); 8.38 (1H, d, J=1.6 Hz, aromatic-H). at reflux for 2 h The solvent was removed under vacuum the residue chromatographed through silica-gel eluting with dichloromethane/ethanol/ammonia (40:8:1)

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

Procedure: A mixture of azetidine (2.0 g, 35.0 mmol), 4-chlorobutanal dimethylacetal (5.88 g, 39.0 mmol) and K2CO3 (5.38 g, 39.0 mmol), in anhydrous DMF (100ml), was stirred at room temperature for 72 h. Water (50 ml) was added and the mixture extracted with EtOAc (3×150 ml). The combined extracts were washed with H2O (3×50ml), dried (Na2SO4) and evaporated. The crude product was purified by distillation (1.2 g). δ (360 MHz, CDCl3) 1.35-1.42 (2H, m, CH2), 1.57-1.64 (2H, m, CH2), 2.00-2.40 (2H, m, CH2), 2.36 (2H, t, J=9.0 Hz, CH2), 3.15 (4H, m, t, J=7.0 Hz, 2 of CH2), 3.33 (6H, s, 2 of OMe), 4.35 (1H, t, J=5.7 Hz, CH). the mixture extracted with EtOAc (3×150 ml) The combined extracts were washed with H2O (3×50ml) dried (Na2SO4) evaporated The crude product was purified by distillation (1.2 g)