(4-methyloxan-4-yl)methanol

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: To a solution of (4-methyl-tetrahydro-pyran-4-yl)-methanol (1.5 g, 11.5 mmol) in CH2Cl2 was added a suspension of Dess-Martin periodinane (5.8 g, 14 mmol) in CH2Cl2 (30 mL). After 70 min, the heterogenous mixture was diluted with Et2O (100 mL), stirred for 10 min, treated with 1 N HaOH (10 mL), and stirred for another 10 min. The mixture was filtered, and the filtrate was concentrated. The residue was purified by chromatography (Et2O/CH2Cl2) to give the title compound (1.01 g, 68%) as a colorless volatile oil. The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. treated with 1 N HaOH (10 mL) stirred for another 10 min The mixture was filtered the filtrate was concentrated The residue was purified by chromatography (Et2O/CH2Cl2)

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

Procedure: A 78° C. solution of 4-methyl-tetrahydro-pyran-4-carboxylic acid methyl ester (Regan, J. et al. J. Med. Chem. 2002, 45, 2994-3008; 9.9 g, 63 mmol) in CH2Cl2 (400 mL) was treated with DIBAL-H (1.0 M in CH2Cl2; 125 mL, 125 mmol). The resulting mixture was stirred for 1 h, and then was diluted with EtOAc (200 mL) and satd. aq. NH4Cl. The mixture was treated with satd. aq. sodium potassium tartrate, allowed to warm to rt, and stirred for 45 min. The mixture was extracted with CH2Cl2 (4×), and the combined extracts were washed with satd. aq. NaCl, dried, and concentrated. Chromatography (EtOAc/hexanes) afforded the title compound as a colorless oil (5.6 g 69%). The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. The mixture was treated with satd stirred for 45 min The mixture was extracted with CH2Cl2 (4×) the combined extracts were washed with satd aq. NaCl, dried concentrated

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

Procedure: A 78° C. solution of 4-methyl-tetrahydro-pyran-4-carboxylic acid methyl ester (Regan, J. et al. J. Med. Chem. 2002, 45, 2994-3008; 9.9 g, 63 mmol) in CH2Cl2 (400 mL) was treated with DIBAL-H (1.0 M in CH2Cl2; 125 mL, 125 mmol). The resulting mixture was stirred for 1 h, and then was diluted with EtOAc (200 mL) and satd. aq. NH4Cl. The mixture was treated with satd. aq. sodium potassium tartrate, allowed to warm to rt, and stirred for 45 min. The mixture was extracted with CH2Cl2 (4×), and the combined extracts were washed with satd. aq. NaCl, dried, and concentrated. Chromatography (EtOAc/hexanes) afforded the title compound as a colorless oil (5.6 g 69%). The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. The mixture was treated with satd stirred for 45 min The mixture was extracted with CH2Cl2 (4×) the combined extracts were washed with satd aq. NaCl, dried concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At −78° C., 73.3 ml (73.3 mmol, 1.0M in toluene) of diisobutylaluminium hydride were added dropwise to a solution of 5.80 g (36.7 mmol) of methyl 4-methyltetrahydro-2H-pyran-4-carboxylate in 220 ml of toluene such that the internal temperature did not exceed −70° C. The mixture was subsequently stirred at −78° C. for another 90 min and then further at room temperature overnight. The reaction was terminated by addition of 40 ml of methanol and 300 ml of 1N hydrochloric acid. The phases were separated and the aqueous phase was extracted three times with 150 ml of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product corresponded to the title compound. Yield: 2.14 g (45% of theory) did not exceed −70° C further at room temperature overnight The reaction was terminated by addition of 40 ml of methanol and 300 ml of 1N hydrochloric acid The phases were separated the aqueous phase was extracted three times with 150 ml of ethyl acetate The combined organic phases were washed with saturated aqueous sodium chloride solution dried over magnesium sulphate filtered the solvent was removed under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At −78° C., 73.3 ml (73.3 mmol, 1.0M in toluene) of diisobutylaluminium hydride were added dropwise to a solution of 5.80 g (36.7 mmol) of methyl 4-methyltetrahydro-2H-pyran-4-carboxylate in 220 ml of toluene such that the internal temperature did not exceed −70° C. The mixture was subsequently stirred at −78° C. for another 90 min and then further at room temperature overnight. The reaction was terminated by addition of 40 ml of methanol and 300 ml of 1N hydrochloric acid. The phases were separated and the aqueous phase was extracted three times with 150 ml of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product corresponded to the title compound. Yield: 2.14 g (45% of theory) did not exceed −70° C further at room temperature overnight The reaction was terminated by addition of 40 ml of methanol and 300 ml of 1N hydrochloric acid The phases were separated the aqueous phase was extracted three times with 150 ml of ethyl acetate The combined organic phases were washed with saturated aqueous sodium chloride solution dried over magnesium sulphate filtered the solvent was removed under reduced pressure

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

Procedure: To a solution of (4-methyl-tetrahydro-pyran-4-yl)-methanol (1.5 g, 11.5 mmol) in CH2Cl2 was added a suspension of Dess-Martin periodinane (5.8 g, 14 mmol) in CH2Cl2 (30 mL). After 70 min, the heterogenous mixture was diluted with Et2O (100 mL), stirred for 10 min, treated with 1 N HaOH (10 mL), and stirred for another 10 min. The mixture was filtered, and the filtrate was concentrated. The residue was purified by chromatography (Et2O/CH2Cl2) to give the title compound (1.01 g, 68%) as a colorless volatile oil. The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. treated with 1 N HaOH (10 mL) stirred for another 10 min The mixture was filtered the filtrate was concentrated The residue was purified by chromatography (Et2O/CH2Cl2)

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

Procedure: A −78° C. solution of 4-methyl-tetrahydro-pyran-4-carboxylic acid methyl ester (Regan, J. et al. J. Med. Chem. 2002, 45, 2994-3008; 9.9 g, 63 mmol) in CH2Cl2 (400 mL) was treated with DIBAL-H (1.0 M in CH2Cl2; 125 mL, 125 mmol). The resulting mixture was stirred for 1 h, and then was diluted with EtOAc (200 mL) and satd. aq. NH4Cl. The mixture was treated with satd. aq. sodium potassium tartrate, allowed to warm to rt, and stirred for 45 min. The mixture was extracted with CH2Cl2 (4×), and the combined extracts were washed with satd. aq. NaCl, dried, and concentrated. Chromatography (EtOAc/hexanes) afforded the title compound as a colorless oil (5.6 g 69%). The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. The mixture was treated with satd stirred for 45 min The mixture was extracted with CH2Cl2 (4×) the combined extracts were washed with satd aq. NaCl, dried concentrated

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

Procedure: A −78° C. solution of 4-methyl-tetrahydro-pyran-4-carboxylic acid methyl ester (Regan, J. et al. J. Med. Chem. 2002, 45, 2994-3008; 9.9 g, 63 mmol) in CH2Cl2 (400 mL) was treated with DIBAL-H (1.0 M in CH2Cl2; 125 mL, 125 mmol). The resulting mixture was stirred for 1 h, and then was diluted with EtOAc (200 mL) and satd. aq. NH4Cl. The mixture was treated with satd. aq. sodium potassium tartrate, allowed to warm to rt, and stirred for 45 min. The mixture was extracted with CH2Cl2 (4×), and the combined extracts were washed with satd. aq. NaCl, dried, and concentrated. Chromatography (EtOAc/hexanes) afforded the title compound as a colorless oil (5.6 g 69%). The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. The mixture was treated with satd stirred for 45 min The mixture was extracted with CH2Cl2 (4×) the combined extracts were washed with satd aq. NaCl, dried concentrated

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

Procedure: To a solution of (4-methyl-tetrahydro-pyran-4-yl)-methanol (1.5 g, 11.5 mmol) in CH2Cl2 was added a suspension of Dess-Martin periodinane (5.8 g, 14 mmol) in CH2Cl2 (30 mL). After 70 min, the heterogenous mixture was diluted with Et2O (100 mL), stirred for 10 min, treated with 1 N HaOH (10 mL), and stirred for another 10 min. The mixture was filtered, and the filtrate was concentrated. The residue was purified by chromatography (Et2O/CH2Cl2) to give the title compound (1.01 g, 68%) as a colorless volatile oil. The spectral data matched that reported in PCT Intl. Pat. Appl. Publ. No. WO 2006/001752. treated with 1 N HaOH (10 mL) stirred for another 10 min The mixture was filtered the filtrate was concentrated The residue was purified by chromatography (Et2O/CH2Cl2)