2-(oxan-4-yl)ethyl methanesulfonate

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: To 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate (5.4 g) in dry acetone at room temperature was added lithium bromide (9 g) in one go. The reaction was heated to reflux for 4 hours, under nitrogen. The reaction was cooled to room temperature and concentrated in vacuo. The residue was taken up in dichloromethane (100 ml) and washed with water (50 ml). The organic layer was dried by passing through a hydrophobic frit, and concentrated in vacuo. The product was purified by silica chromatography (40 g) (ISCO) using a gradient elution of 0-50% cyclohexane:ethyl acetate to afford the title compound as a colourless oil (3.5 g). The reaction was heated to reflux for 4 hours, under nitrogen concentrated in vacuo washed with water (50 ml) The organic layer was dried concentrated in vacuo The product was purified by silica chromatography (40 g) (ISCO) a gradient elution of 0-50% cyclohexane

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

Procedure: To 2-(tetrahydro-2H-pyran-4-yl)ethanol (3,3 g) in dry dichloromethane (100 ml) at 0° C. and under nitrogen was added triethylamine (4.6 ml), followed by methanesulphonyl chloride (2.6 ml) dropwise over 5 minutes. The reaction was stirred until the ice in the bath melted and left overnight at room temperature. The reaction was washed with saturated aqueous sodium bicarbonate (40 ml). The organic layer was dried by passing through a hydrophobic frit and concentrated in vacuo to yield the title compound as a yellow oil (5.4 g). The reaction was washed with saturated aqueous sodium bicarbonate (40 ml) The organic layer was dried concentrated in vacuo

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

Procedure: To 2-(tetrahydro-2H-pyran-4-yl)ethanol (3,3 g) in dry dichloromethane (100 ml) at 0° C. and under nitrogen was added triethylamine (4.6 ml), followed by methanesulphonyl chloride (2.6 ml) dropwise over 5 minutes. The reaction was stirred until the ice in the bath melted and left overnight at room temperature. The reaction was washed with saturated aqueous sodium bicarbonate (40 ml). The organic layer was dried by passing through a hydrophobic frit and concentrated in vacuo to yield the title compound as a yellow oil (5.4 g). The reaction was washed with saturated aqueous sodium bicarbonate (40 ml) The organic layer was dried concentrated in vacuo

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

Procedure: The product of Example 8A (2.9 mmol), triethylamine (1.2 mL, 8.7 mmol) and methanesulfonyl chloride (0.34 mL, 4.4 mmol) in 10 mL tetrahydrofuran (THF) were reacted and the product isolated as in Example 1C to give the title compound that was used directly in the next reaction. the product isolated as in Example 1C

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

Procedure: The product of Example 8A (2.9 mmol), triethylamine (1.2 mL, 8.7 mmol) and methanesulfonyl chloride (0.34 mL, 4.4 mmol) in 10 mL tetrahydrofuran (THF) were reacted and the product isolated as in Example 1C to give the title compound that was used directly in the next reaction. the product isolated as in Example 1C

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: The product of Example 8A (2.9 mmol), triethylamine (1.2 mL, 8.7 mmol) and methanesulfonyl chloride (0.34 mL, 4.4 mmol) in 10 mL tetrahydrofuran (THF) were reacted and the product isolated as in Example 1C to give the title compound that was used directly in the next reaction. the product isolated as in Example 1C

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

Procedure: Following the general procedure III as described above, the alkylation of 1′-[(6-chloro-1H-indol-3-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine] (prepared according to example 69) with commercially available methanesulfonic acid 2-(tetrahydro-pyran-4-yl)-ethylester (described in US 2004220214) gave the title compound in 55% yield. ES-MS m/e (%): 465.2(M+H+).

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

Procedure: Following the general procedure III as described above, the alkylation of 1′-[(6-chloro-1H-indol-3-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine] (prepared according to example 69) with commercially available methanesulfonic acid 2-(tetrahydro-pyran-4-yl)-ethyl ester (described in US 2004220214) gave the title compound in 55% yield. ES-MS m/e (%): 465.2 (M+H+).