2-(4-chlorobutoxy)oxane

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

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

Procedure: (bbb) In an analogous manner to that described in Example 44 (e), by alkylating tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate [Example 46 (b)] with 2-(4-chloro-butoxy)-tetrahydro-2H-pyran there was obtained a mixture of tert-butyl (3RS,4RS)- and (3SR,4SR)-3-hydroxy-4-[4-[4-[(RS)-tetrahydropyran-2-yloxy]-butoxy]-phenyl]-piperidine-1-carboxylate, alkylation of which with 2-bromomethyl-naphthalene analogously to Example 1 (g) gave a mixture of (3RS,4RS)- and (3SR,4SR)-3-(naphthalen-2-ylmethoxy)-4-[4-[4-[(RS)-tetrahydro-pyran-2-yloxy]-butoxy]-phenyl]-piperidine-1-carboxylate. Cleavage of the THP group with hydrogen chloride in methanol analogously to Example 53 (c) yielded tert-butyl (3RS,4RS)-4-[4-(4-hydroxy-butoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine1-carboxylate, alkylation of which with benzyl bromide analogously to Example 1 (g) gave tert-butyl (3RS,4RS)-4-[4-(4-benzyloxy-butoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless oil; MS: 613 (M+NH4)+. there was obtained gave

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

Procedure: (bbb) In an analogous manner to that described in Example 44 (e), by alkylating tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate [Example 46 (b)] with 2-(4-chloro-butoxy)-tetrahydro-2H-pyran there was obtained a mixture of tert-butyl (3RS,4RS)- and (3SR,4SR)-3-hydroxy-4-[4-[4-[(RS)-tetrahydropyran-2-yloxy]-butoxy]-phenyl]-piperidine-1-carboxylate, alkylation of which with 2-bromomethyl-naphthalene analogously to Example 1 (g) gave a mixture of (3RS,4RS)- and (3SR,4SR)-3-(naphthalen-2-ylmethoxy)-4-[4-[4-[(RS)-tetrahydro-pyran-2-yloxy]-butoxy]-phenyl]-piperidine-1-carboxylate. Cleavage of the THP group with hydrogen chloride in methanol analogously to Example 53 (c) yielded tert-butyl (3RS,4RS)-4-[4-(4-hydroxy-butoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine1-carboxylate, alkylation of which with benzyl bromide analogously to Example 1 (g) gave tert-butyl (3RS,4RS)-4-[4-(4-benzyloxy-butoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless oil; MS: 613 (M+NH4)+. there was obtained gave

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colourless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml) The dried liquid was heated under reduced pressure

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colourless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml) The dried liquid was heated under reduced pressure

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18 M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colorless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1M, 50 ml) and BR (50 ml) The dried liquid was heated under reduced pressure

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

Procedure: 27 g of ethyldiisopropylamine, 18 g of lithium bromide and 46 g of 2-(4-chlorobutoxy) tetrahydropyran (86.3% pure according to GC) were added to 36.3 g of 3-methyl-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione in 1 l of dimethylformamide, with stirring, and the mixture was stirred for 5 h at 70° C. It was concentrated under reduced pressure and 34.5 g of crude 3-methyl-6-[4-(tetrahydropyran-2-yloxy)butyl]-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione were obtained after working-up of the residue by extraction with dichloromethane and water and after drying and concentration of the combined dichloromethane phases, and this crude product was purified by column chromatography on aluminum oxide (actiVity grade III) and elution with dichloromethane/ethanol (volume ratio 90:10). the mixture was stirred for 5 h at 70° C It was concentrated under reduced pressure

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

Procedure: 27 g of ethyldiisopropylamine, 18 g of lithium bromide and 46 g of 2-(4-chlorobutoxy) tetrahydropyran (86.3% pure according to GC) were added to 36.3 g of 3-methyl-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione in 1 l of dimethylformamide, with stirring, and the mixture was stirred for 5 h at 70° C. It was concentrated under reduced pressure and 34.5 g of crude 3-methyl-6-[4-(tetrahydropyran-2-yloxy)butyl]-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione were obtained after working-up of the residue by extraction with dichloromethane and water and after drying and concentration of the combined dichloromethane phases, and this crude product was purified by column chromatography on aluminum oxide (actiVity grade III) and elution with dichloromethane/ethanol (volume ratio 90:10). the mixture was stirred for 5 h at 70° C It was concentrated under reduced pressure

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1M, 50ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colourless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1M, 50ml) and BR (50 ml) The dried liquid was heated under reduced pressure

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18 M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1 M, 50 ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colourless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1 M, 50 ml) and BR (50 ml) The dried liquid was heated under reduced pressure

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

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

Procedure: Dihydropyran (15.5 g) was added dropwise to a mixture of 4-chlorobutanol (20 g) and hydrochloric acid (18 M, 1 drop) at RT. The mixture was stirred for 30 min and washed with H2O (100 ml), aqueous NaHCO3 (1 M, 50 ml) and BR (50 ml). The dried liquid was heated under reduced pressure to leave the title compound as a colourless liquid (31.9 g). T.l.c. [L] Rf 0.5. washed with H2O (100 ml), aqueous NaHCO3 (1 M, 50 ml) and BR (50 ml) The dried liquid was heated under reduced pressure