1,2-diphenylethanol

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

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

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 12.0 (60.5 mmol) of 1,2-diphenylethanol in 50 mL of dry diethyl ether, 11.0 g (3.80 mL, 40.0 mmol) of PBr3 was added with vigorous stirring at −10° C. The resulting mixture was stirred for 12 hr at room temperature and then added to 350 mL of cold water. The organic layer was separated, and the aqueous layer was extracted with 2×100 mL of water. The combined organic extracts were washed with aqueous NaHCO3, dried over Na2SO4, and evaporated to dryness. This procedure gave 13.2 g (84%) of the title product. The resulting mixture was stirred for 12 hr at room temperature The organic layer was separated the aqueous layer was extracted with 2×100 mL of water The combined organic extracts were washed with aqueous NaHCO3 dried over Na2SO4 evaporated to dryness

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 100 mL (0.10 mol) of 1.0 M BnMgBr in THF 9.50 g (90 mmol) of benzaldehyde (2) was added with vigorous stirring at −10° C. This mixture was slowly warmed to room temperature and then stirred for 2 hr at this temperature. The mixture was added to 300 mL of saturated aqueous Na2SO4. The organic layer was separated and washed with saturated aqueous NH4Cl. The aqueous layer was extracted with 2×100 mL of diethyl ether. The combined organic extracts were evaporated to dryness, and the residue was dissolved in 100 mL of dichloromethane. The obtained solution was dried over Na2SO4 and evaporated to dryness. This crude product was further used without an additional purification. Yield 12.0 g (67%) of the title compound. This mixture was slowly warmed to room temperature stirred for 2 hr at this temperature The organic layer was separated washed with saturated aqueous NH4Cl The aqueous layer was extracted with 2×100 mL of diethyl ether The combined organic extracts were evaporated to dryness the residue was dissolved in 100 mL of dichloromethane The obtained solution was dried over Na2SO4 evaporated to dryness This crude product was further used without an additional purification

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

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 12.0 (60.5 mmol) of 1,2-diphenylethanol in 50 mL of dry diethyl ether, 11.0 g (3.80 mL, 40.0 mmol) of PBr3 was added with vigorous stirring at −10° C. The resulting mixture was stirred for 12 hr at room temperature and then added to 350 mL of cold water. The organic layer was separated, and the aqueous layer was extracted with 2×100 mL of water. The combined organic extracts were washed with aqueous NaHCO3, dried over Na2SO4, and evaporated to dryness. This procedure gave 13.2 g (84%) of the title product. The resulting mixture was stirred for 12 hr at room temperature The organic layer was separated the aqueous layer was extracted with 2×100 mL of water The combined organic extracts were washed with aqueous NaHCO3 dried over Na2SO4 evaporated to dryness

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 100 mL (0.10 mol) of 1.0 M BnMgBr in THF 9.50 g (90 mmol) of benzaldehyde (2) was added with vigorous stirring at −10° C. This mixture was slowly warmed to room temperature and then stirred for 2 hr at this temperature. The mixture was added to 300 mL of saturated aqueous Na2SO4. The organic layer was separated and washed with saturated aqueous NH4Cl. The aqueous layer was extracted with 2×100 mL of diethyl ether. The combined organic extracts were evaporated to dryness, and the residue was dissolved in 100 mL of dichloromethane. The obtained solution was dried over Na2SO4 and evaporated to dryness. This crude product was further used without an additional purification. Yield 12.0 g (67%) of the title compound. This mixture was slowly warmed to room temperature stirred for 2 hr at this temperature The organic layer was separated washed with saturated aqueous NH4Cl The aqueous layer was extracted with 2×100 mL of diethyl ether The combined organic extracts were evaporated to dryness the residue was dissolved in 100 mL of dichloromethane The obtained solution was dried over Na2SO4 evaporated to dryness This crude product was further used without an additional purification

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

Procedure: To a flame-dried flask containing a near-solution of 810 mg of 4-hydroxycoumarin and 1.20 mg of 1,2-diphenylethanol of Preparation 15 in 30 mL of dioxane under an argon atmosphere is added 3.0 mL of boron trifluoride etherate. The resulting yellow solution is left to stir at room temperature overnight; the reaction is then heated to reflux for 48 hours. The volatiles are removed and the residue is partioned between diethyl ether and 1N sodium hydroxide. The basic aqueous phase is washed with diethyl ether and acidified to pH=1 with 6N hydrochloric acid. The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents). The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin, then brine, dried (magnesium sulfate), and finally concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed with 40% to 50% ethyl acetate in hexanes to yield 167 mg of the title product as a white solid. To a flame-dried flask containing The resulting yellow solution is left the reaction is then heated to reflux for 48 hours The volatiles are removed The basic aqueous phase is washed with diethyl ether The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents) The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin brine, dried (magnesium sulfate) finally concentrated under reduced pressure chromatographed with 40% to 50% ethyl acetate in hexanes

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

Procedure: To a stirring suspension of 1.20 g of lithium aluminum hydride in 100 mL of diethyl ether under an argon atmosphere at 0° C. Is slowly added a solution of 5.50 g of commercially available deoxybenzoin in 25.0 mL of diethyl ether. After 0.5 hours the grey suspension is warmed to room temperature. After 1 hour the reaction mixture is re-cooled to 0° C. and slowly treated with 1.25 mL of water followed by 5.50 mL of 1N sodium hydroxide. After 0.5 hour the resulting white precipitant is filtered through a pad of magnesium sulfate with diethyl ether washings. The filtrate is concentrated under reduced pressure to afford 5.50 g of the title product as off-white crystals. This product may be used directly in the next reaction without further purification. After 1 hour the reaction mixture is re-cooled to 0° C. After 0.5 hour the resulting white precipitant is filtered through a pad of magnesium sulfate with diethyl ether washings The filtrate is concentrated under reduced pressure

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

Procedure: Oxalyl dichloride (141 μl, 1.67 mmol) was added dropwise to a solution of 1-methylpiperidine-4-carboxylic acid hydrochloride (300 mg, 1.67 mmol) in DCM (20 ml) and few drops of DMF (catalytic amount). The reaction was stirred at room temperature for 2 hours. The volatiles were removed under vacuum, and the crude was taken up with pyridine (20 ml). 1,2-Diphenylethanol (331 mg, 1.67 mmol) was added, and the resulting suspension was heated under microwave irradiation at 140° C. for 1 hour. Pyridine was removed under vacuum, and the crude was purified by flash chromatography (DCM/MeOH=97/3 to 94/6) to obtain 1,2-diphenylethyl 1-methylpiperidine-4-carboxylate (200 mg). The volatiles were removed under vacuum the resulting suspension was heated under microwave irradiation at 140° C. for 1 hour Pyridine was removed under vacuum the crude was purified by flash chromatography (DCM/MeOH=97/3 to 94/6)

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

Procedure: Quinuclidine-3-carboxylic acid hydrochloride (160 mg, 0.83 mmol), EDC (290 mg, 1.51 mmol), and HOBT (232 mg, 1.51 mmol) were dissolved in dry DMF (8 ml). 1,2-Diphenylethanol (150 mg, 0.76 mmol) and TEA (0.32 ml, 2.27 mmol) were added, and the resulting mixture was stirred at room temperature overnight. Then quinuclidine-3-carboxylic acid hydrochloride (72.5 mg, 0.38 mmol), EDC (87 mg, 0.45 mmol), and HOBT (57.9 mg, 0.38 mmol) were added followed by TEA (0.16 ml, 1.13 mmol), and the mixture was stirred for additional 32 hours. The mixture was diluted with water and extracted three times with Et2O. The organic phases were collected, washed with brine, dried over Na2SO4, filtered, and evaporated to dryness. The crude residue was purified by flash chromatography (DCM/MeOH=9/1) to obtain 1,2-diphenylethyl quinuclidine-3-carboxylate (136 mg, racemic mixture). the mixture was stirred for additional 32 hours extracted three times with Et2O The organic phases were collected washed with brine dried over Na2SO4 filtered evaporated to dryness The crude residue was purified by flash chromatography (DCM/MeOH=9/1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.33 ml of a 1.6-molar solution of n-butyllithium (2.13 mmol) in pentane were added dropwise at room temperature under argon for 2 minutes to a stirred solution of 500 mg (2.13 mmol) 3-benzyl-2,2,4,4-tetramethyl-3-pentanol in 4 ml THF. The solution obtained was stirred for 30 minutes, then 275 μl (2.13 mmol) benzaldehyde, 290 mg (2.13 mmol) ZnCl2 and 2 ml HMPA were added. The reaction mixture was heated to 70° C. and stirred for 4 hours at this temperature. Subsequently, it was cooled to room temperature and processed analogous to Example 1. The raw product obtained was cleaned by means of a silica column with 35% diethyl ether/light gasoline. There was obtained the alcohol as a colorless oil. The solution obtained stirred for 4 hours at this temperature Subsequently, it was cooled to room temperature The raw product obtained