[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methanol

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Toluene-4-sulphonyl chloride (4.2 g) was added at -10° C. under nitrogen to a stirred solution of (S)-1,4-benzodioxan-2-ylmethanol (3.3 g) in pyridine (50 ml) The mixture was allowed to warm to ambient temperature and was stirred for a further 60 hours, then poured onto ice-water (200 ml). The product was extracted into ethyl acetate (3×200 ml) then the combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml), dried over magnesium sulphate, and the solvent removed in vacuo. The resulting orange oil (5.84 g), which solidified slowly on standing, was purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture to yield two batches of a white crystalline solid (2.4 and 1.2 g). The 2.4 g batch was recrystallised 3 times from ethanol, the solid obtained becoming each time less rich in the desired (R)-isomer of the product and was therefore discarded. The mother liquors from these 3 recrystallisations now contained predominantly the desired (R)-isomer of the product so they were combined, the solvent removed in vacuo and the residue recrystallised from ethanol to yield white crystals of (R)-1,4-benzodioxan-2-ylmethyl toluene-4-sulphonate (1.2 g); m.p. 105°-107° C. poured onto ice-water (200 ml) The product was extracted into ethyl acetate (3×200 ml) the combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml) dried over magnesium sulphate the solvent removed in vacuo was purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture to yield two batches of a white crystalline solid (2.4 and 1.2 g) The 2.4 g batch was recrystallised 3 times from ethanol the solid obtained The mother liquors from these 3 recrystallisations the solvent removed in vacuo the residue recrystallised from ethanol

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

Procedure: Toluene-4-sulphonyl chloride (4.2 g) was added at -10° C. under nitrogen to a stirred solution of (S)-1,4-benzodioxan-2-ylmethanol (3.3 g) in pyridine (50 ml) The mixture was allowed to warm to ambient temperature and was stirred for a further 60 hours, then poured onto ice-water (200 ml). The product was extracted into ethyl acetate (3×200 ml) then the combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml), dried over magnesium sulphate, and the solvent removed in vacuo. The resulting orange oil (5.84 g), which solidified slowly on standing, was purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture to yield two batches of a white crystalline solid (2.4 and 1.2 g). The 2.4 g batch was recrystallised 3 times from ethanol, the solid obtained becoming each time less rich in the desired (R)-isomer of the product and was therefore discarded. The mother liquors from these 3 recrystallisations now contained predominantly the desired (R)-isomer of the product so they were combined, the solvent removed in vacuo and the residue recrystallised from ethanol to yield white crystals of (R)-1,4-benzodioxan-2-ylmethyl toluene-4-sulphonate (1.2 g); m.p. 105°-107° C. poured onto ice-water (200 ml) The product was extracted into ethyl acetate (3×200 ml) the combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml) dried over magnesium sulphate the solvent removed in vacuo was purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture to yield two batches of a white crystalline solid (2.4 and 1.2 g) The 2.4 g batch was recrystallised 3 times from ethanol the solid obtained The mother liquors from these 3 recrystallisations the solvent removed in vacuo the residue recrystallised from ethanol

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: Catechol (13.2 g, 0.12 mol) and potassium carbonate (16.6 g, 0.12 mol) were stirred in DMF (250 mL) and (2R)-glycidyl tosylate (22.8 g, 0.10 mol) was added and the reaction was stirred at 60° C. for 24 h. The reaction was cooled to room temperature and diluted with ice water (1 L) and extracted with diethyl ether (4 times). The combined organic solution was washed 3 times with 10% potassium carbonate, once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1) to yield ((2S)-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol as a solid. The reaction was cooled to room temperature extracted with diethyl ether (4 times) The combined organic solution was washed 3 times with 10% potassium carbonate once with water, once with brine and evaporated in vacuo to yield a white solid which was purified by flash column chromatography (DCM:Methanol—50:1)

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

Procedure: (S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)-methanol (24.1 mmol, 4.0 g), triethylamine (24.3 mmol, 3.42 ml) and DCM (50 ml) were mixed and stirred on an ice-bath. p-Toluenesulfonyl chloride (24.3 mmol, 4.63 g) in DCM (10 ml) was added dropwise. The mixture was stirred over night at r.t and washed with water. The organic phase was evaporated to dryness. The crude product was dissolved in THF (10 ml) and treated with 1 M NaOH (2 ml) for 10 minutes. Water (100 ml) was added. The aqueous solution was extracted with EtOAc, the organic phase was dried and evaporated to dryness. Flash chromatography, using heptane/EtOAc as eluent gave 7.66 g of the desired product. The mixture was stirred over night at r.t washed with water The organic phase was evaporated to dryness The crude product was dissolved in THF (10 ml) treated with 1 M NaOH (2 ml) for 10 minutes Water (100 ml) was added The aqueous solution was extracted with EtOAc the organic phase was dried evaporated to dryness

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

Procedure: (S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)-methanol (24.1 mmol, 4.0 g), triethylamine (24.3 mmol, 3.42 ml) and DCM (50 ml) were mixed and stirred on an ice-bath. p-Toluenesulfonyl chloride (24.3 mmol, 4.63 g) in DCM (10 ml) was added dropwise. The mixture was stirred over night at r.t and washed with water. The organic phase was evaporated to dryness. The crude product was dissolved in THF (10 ml) and treated with 1 M NaOH (2 ml) for 10 minutes. Water (100 ml) was added. The aqueous solution was extracted with EtOAc, the organic phase was dried and evaporated to dryness. Flash chromatography, using heptane/EtOAc as eluent gave 7.66 g of the desired product. The mixture was stirred over night at r.t washed with water The organic phase was evaporated to dryness The crude product was dissolved in THF (10 ml) treated with 1 M NaOH (2 ml) for 10 minutes Water (100 ml) was added The aqueous solution was extracted with EtOAc the organic phase was dried evaporated to dryness

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

Procedure: (R)-2,3-Dihydro-benzo[1,4]dioxine-2-carboxylic acid (27.9 mmol, 5.02 g) was dissolved in dry THF (30 ml). LiAlH4 (56.9 mmol, 2.16 g) was added. The mixture was refluxed for 70 minutes. After cooling, the reaction was quenched with water and 1 M NaOH. The mixture was filtrated through Celite and evaporated to dryness. This gave 4.3 g of the title compound. The mixture was refluxed for 70 minutes After cooling the reaction was quenched with water and 1 M NaOH The mixture was filtrated through Celite evaporated to dryness