tert-Butyl 4-chlorobutylcarbamate

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: This compound, employed as the starting material in example 2, is prepared by following substantially the same procedure described above under (a) but using 4-chloro-butylamine hydrochloride instead of 3-chloro-propylamine hydrochloride. is prepared

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 1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine HCl (1:1) (0.02 mol), 1,1-dimethylethyl (4-chlorobutyl)carbamate (0.044 mol), Na2CO3 (0.05 mol) and KI (catalytic quantity) in 4-methyl-2-pentanone (200 ml) was stirred and refluxed overnight, then cooled to room temperature and the solvent was evaporated. The residue was washed with water and extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10). The desired fractions were collected and the solvent was evaporated, yielding 1,1-dimethylethyl [4-(3,4-dihydro[1]benzothieno[3,2-c]pyridine-2(1H)-yl)butyl]carbamate (intern 1). refluxed overnight the solvent was evaporated The residue was washed with water extracted with CH2Cl2 The separated organic layer was dried filtered the solvent evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10) The desired fractions were collected the solvent was evaporated

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

Procedure: A mixture of 1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine HCl (1:1) (0.02 mol), 1,1-dimethylethyl (4-chlorobutyl)carbamate (0.044 mol), Na2CO3 (0.05 mol) and KI (catalytic quantity) in 4-methyl-2-pentanone (200 ml) was stirred and refluxed overnight, then cooled to room temperature and the solvent was evaporated. The residue was washed with water and extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10). The desired fractions were collected and the solvent was evaporated, yielding 1,1-dimethylethyl [4-(3,4-dihydro[1]benzothieno[3,2-c]pyridine-2(1H)-yl)butyl]carbamate (intern 1). refluxed overnight the solvent was evaporated The residue was washed with water extracted with CH2Cl2 The separated organic layer was dried filtered the solvent evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10) The desired fractions were collected the solvent was evaporated

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

Procedure: N-[(tert-butoxy)carbonyl]-4-chloro-butylamine (2.5 g, 0.012 mol) is then gradually added to the resulting mixture at room temperature. The reaction mixture is stirred at room temperature for 2 hours and at the reflux temperature for 6 hours, and then poured into ethyl acetate/water (1/1, v/v) (100 ml). The organic phase is separated, washed several times with water, and dried over MgSO4. The organic phase is separated washed several times with water dried over MgSO4

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Metallic sodium (0.28 g, 0.012 mol) is dissolved in absolute ethyl alcohol (EtOH) (9 ml) under nitrogen atmosphere. The mixture is heated to 60° C. and diethyl malonate (3.8 g, 0.024 mol) is then dripped therein. N-tert-butoxycarbonyl-4-chloro-butylamine (2.5 g, 0.012 mol) is then gradually added, at room temperature, to the resulting solution. The reaction mixture is stirred at room temperature for 2 hours and at the reflux temperature for 6 hours, and then poured into a mixture AcOEt/water (100 ml 1/1 v/v). The organic phase which is separated is then washed repeatedly with water and dried over MgSO4The solvent is removed under vacuum at 100° C. affording a crude oily product which is purified by reverse-phase HPLC on an RP-18 column eluting with an aqueous phase modified with CH3CN (45% by volume). The desired compound (1.31 g) is thus obtained as a pure product. The organic phase which is separated is then washed repeatedly with water dried over MgSO4The solvent is removed under vacuum at 100° C. affording a crude oily product which is purified by reverse-phase HPLC on an RP-18 column eluting with an aqueous phase

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

Procedure: A mixture of 1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine HCl (1:1) (0.02 mol), 1,1-dimethylethyl (4chlorobutyl)carbamate (0.044 mol), Na2CO3 (0.05 mol) and KI (catalytic quantity) in 4-methyl-2-pentanone (200 ml) was stirred and refluxed overnight, then cooled to room temperature and the solvent was evaporated. The residue was washed with water and extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10). The desired fractions were collected and the solvent was evaporated, yielding 1,1-dimethylethyl [4-(3,4-dihydro[1]benzothieno[3,2-c]pyridine-2(1H)-yl)butyl]carbamate (interim.1). refluxed overnight the solvent was evaporated The residue was washed with water extracted with CH2Cl2 The separated organic layer was dried filtered the solvent evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10) The desired fractions were collected the solvent was evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Metallic sodium (0.28 g, 0.012 mol) is dissolved in absolute ethyl alcohol (EtOH) (9 ml) under nitrogen atmosphere. The mixture is heated to 60° C. and diethyl malonate (3.8 g, 0.024 mol) is then dripped therein. N-tert-butoxycarbonyl-4-chloro-butylamine (2.5 g, 0.012 mol) is then gradually added, at room temperature, to the resulting solution. The reaction mixture is stirred at room temperature for 2 hours and at the reflux temperature for 6 hours, and then poured into a mixture AcOEt/water (100 ml 1/1 v/v). The organic phase which is separated is then washed repeatedly with water and dried over MgSO4. The organic phase which is separated is then washed repeatedly with water dried over MgSO4