(3-propan-2-yloxyphenyl)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:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 3-hydroxybenzoate (500 mg) in dimethylformamide (5 ml), 0.463 ml of 2-bromopropane and 197 mg of sodium hydride were added under ice-cooling, and the reaction solution was stirred at room temperature for 5 hours. To the reaction solution was added 10% aqueous citric acid, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil. To a solution of lithium aluminum hydride (250 mg) in tetrahydrofuran (3 ml), a solution of the crude product in tetrahydrofuran (2 ml) was added under ice-cooling, and the reaction solution was stirred at room temperature for 1 hour. To the reaction solution was added sodium sulfate decahydrate, and the mixture was stirred at the same temperature for 1 hour. The reaction solution was Celite-filtered, and the filtrate was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-30:70)) to afford the title compound as a colorless oil. cooling the mixture was extracted with ethyl acetate The combined organic layers were washed with a saturated saline solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil cooling the reaction solution was stirred at room temperature for 1 hour the mixture was stirred at the same temperature for 1 hour The reaction solution was Celite-filtered the filtrate was distilled off under reduced pressure The residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-30:70))

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

Procedure: To m-isopropoxybenzaldehyde (38 g, 0.23 mol) in 500 mL of ethanol was added slowly sodium borohydride (12.2 g, 0.32 mol) over a period of 1 h and the mixture was stirred for 2 h, filtered, and concentrated to 100 mL of its volume. The above mixture was diluted with 50 mL of water, neutralized with sulfuric acid solution with cooling, and was extracted with ether (4×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford 36.32 g (95%) of m-isopropoxybenzyl alcohol. filtered concentrated to 100 mL of its volume The above mixture was diluted with 50 mL of water with cooling was extracted with ether (4×100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of methyl 3-hydroxybenzoate (500 mg) in dimethylformamide (5 ml), 0.463 ml of 2-bromopropane and 197 mg of sodium hydride were added under ice-cooling, and the reaction solution was stirred at room temperature for 5 hours. To the reaction solution was added 10% aqueous citric acid, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil. To a solution of lithium aluminum hydride (250 mg) in tetrahydrofuran (3 ml), a solution of the crude product in tetrahydrofuran (2 ml) was added under ice-cooling, and the reaction solution was stirred at room temperature for 1 hour. To the reaction solution was added sodium sulfate decahydrate, and the mixture was stirred at the same temperature for 1 hour. The reaction solution was Celite-filtered, and the filtrate was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-30:70)) to afford the title compound as a colorless oil. cooling the mixture was extracted with ethyl acetate The combined organic layers were washed with a saturated saline solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil cooling the reaction solution was stirred at room temperature for 1 hour the mixture was stirred at the same temperature for 1 hour The reaction solution was Celite-filtered the filtrate was distilled off under reduced pressure The residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-30:70))

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

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

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-hydroxybenzyl alcohol (2.00 g, 0.014 mol), 2-iodopropane (2.4 ml, 8.29 mmol), cesium carbonate (8.00 g, 0.0246 mol) in DMF (10 ml) was heated at 85° C. for 8 h. The reaction was diluted with water (100 ml) and extracted with DCM (30 ml) and this was washed with water (2×30 ml). The product was chromatographed on silica using DCM:methanol (19:1) to afford 3-isopropoxybenzyl alcohol (1.70 g, 73%) as an orange liquid. extracted with DCM (30 ml) this was washed with water (2×30 ml) The product was chromatographed on silica

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-(hydroxymethyl)phenol (10 g) and potassium carbonate (27.2 g) in DMF (100 ml) was added 2-bromo-propane (14.8 g), the reaction was heated to 90° C. overnight. The reaction mixture was filtered and the filtrate was concentrated and purified by chromatography on silica gel, eluting with petrol:ethyl acetate=5:1. The reaction mixture was filtered the filtrate was concentrated purified by chromatography on silica gel eluting with petrol

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

Procedure: To m-isopropoxybenzaldehyde (38 g, 0.23 mol) in 500 mL of ethanol was added slowly sodium borohydride (12.2 g, 0.32 mol) over a period of 1 h and the mixture was stirred for 2 h, filtered, and concentrated to 100 mL of its volume. The above mixture was diluted with 50 mL of water, neutralized with sulfuric acid solution with cooling, and was extracted with ether (4×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford 36.32 g (95%) of m-isopropoxybenzyl alcohol. filtered concentrated to 100 mL of its volume The above mixture was diluted with 50 mL of water with cooling was extracted with ether (4×100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 30 g (0.18 mol) of 3-isopropoxybenzyl alcohol in 600 ml of ether cooled to -20° C. was added in portions 38.7 ml (0.387 mol) of n-butyllithium (10M) in hexane over a 20 min period, and the reaction mixture was allowed to warm to room temperature and stirred for 2 hr. The above reaction mixture was cooled to -20° C., 23.1 g (0.216 mol) of pyridine-2-carboxaldehyde was added in one portion to the mixture, and the resulting reaction mixture was allowed to warm to room temperature and stirred for 1 hr. Ammonium chloride solution (200 ml) and 100 ml of ethyl acetate were added to the mixture. The resulting mixture was separated, the aqueous layer was extracted with methylene chloride (2×200 ml), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated. The diol was purified by chromatography on silica gel eluting with ethyl acetate/hexane (9:1; and 0.05 % TEA). The solvent was concentrated in vacuo, the brown oil was dissolved in methylene chloride/hexane, and removal of methylene chloride in vacuo to 1/2 of its volume afforded 11.1 g (22.6%) of 2-[1-hydroxy-(6'-hydroxymethyl-2'-isopropoxy) -benzyl]pyridine (Formula XIII: R1 =R7 =H; R2 =2'--OCH (CH3)2), as a tan solid. to warm to room temperature The above reaction mixture was cooled to -20° C. the resulting reaction mixture to warm to room temperature stirred for 1 hr The resulting mixture was separated the aqueous layer was extracted with methylene chloride (2×200 ml) the combined organic layer was washed with brine dried over sodium sulfate concentrated The diol was purified by chromatography on silica gel eluting with ethyl acetate/hexane (9:1; and 0.05 % TEA) The solvent was concentrated in vacuo the brown oil was dissolved in methylene chloride/hexane removal of methylene chloride in vacuo to 1/2 of its volume

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

Procedure: To a solution of 3-Isopropoxy-benzaldehyde 14-1 (20 g, 122 mmol) in methanol (400 mL), sodium borohydride (5 g) is added in several portions at 0° C. The resulting mixture is then stirred at rt for 3 h. The reaction is quenched by addition of saturated NH4OH. Extracted (EtOAc), concentrated, a colorless oil 14-2 (MH+, 166) is obtained and use without purification. Re-dissolve (3-Isopropoxy-phenyl)-methanol 14-2 in ether (244 mL) PBr3 (11.5 mL, 122 mmol) is added dropwise at 0° C. The reaction mixture is stirred at 0° C. then rt for 3 h, quenched (MeOH), extracted (EtOAc), concentrated, a colorless oil 14-3 is obtained. (MH+, 288) The reaction is quenched by addition of saturated NH4OH Extracted (EtOAc) concentrated