4-aminocyclohexan-1-ol;hydrochloride

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: 75.5 g (0.5 Mol) of 4-aminocyclohexanolhydrochloride and 74.0 g (0.5 Mol) of phthalic acid anhydride are mixed with 65 g (0.5 Mol) of ethyl-diisopropyl-amine and 1000 ml of toluene and boiled for 36 hours with a water separator. Then water is added, the toluene phase is separated off and the aqueous phase is extracted several times with chloroform. The organic phases are combined, dried and concentrated. The concentration residue is recrystallised from isopropanol. the toluene phase is separated off the aqueous phase is extracted several times with chloroform dried concentrated The concentration residue is recrystallised from isopropanol

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (2.52 g, 16.6 mmol) in water (20.0 mL) was treated with N-carbethoxyphthalimide (3.82 g, 17.4 mmol) and Na2CO3 (3.77 g, 35.6 mmol). The reaction was stirred at room temperature for 15.6 hours. The reaction was cooled to 0° C. and quenched with 10% HCl, filtered, and washed with water to give a white solid. The solid was dissolved in ethyl acetate washed with water, brine, dried over MgSO4 and concentrated in vacuo to give 3.10 g (76%) of 2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione as a colorless solid: mp 176.9-177.0° C.; 1H NMR (400 MHz, Acetone-d6) δ 7.82 4.09, 3.74, 3.62, 2.28, 2.04, 1.76, 1.39; 13C NMR (100 MHz, acetone-d6) δ 168.7, 135.1, 133.0, 123.6, 69.5, 50.8, 35.7, 28.3; IR (mull) 3389, 3318, 2953, 2930, 2876, 2861, 1767, 1703, 1463, 1393, 1377, 1088, 1075, 1061, 720 cm−1; HRMS (FAB) calcd for C14H16NO3: 246.1130, found 246.1128; Anal. Calcd for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.39; H, 6.21; N, 5.70. The reaction was cooled to 0° C. quenched with 10% HCl filtered washed with water to give a white solid washed with water, brine dried over MgSO4 concentrated in vacuo

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

Procedure: 2-(4-Fluoro-3-nitrophenyl)benzoxazole (see Working Example 15-2) (0.60 g, 2.3 mmol) was added to an acetonitrile (20 mL) solution containing triethylamine (0.70 g, 7.0 mmol) and 4-aminocyclohexanol hydrochloride (0.53 g, 2.5 mmol), and this was heated to reflux for 2 hours with stirring. After the reaction was complete, this was cooled to room temperature, and the crystals precipitated by the addition of water were filtered. After the crystals were washed with water, they were dried under reduced pressure with heating to give crystals that were added to a solution of a solvent mixture of methanol/tetrahydrofuran (1:1, 20 mL) including 10% palladium-carbon (50 mg). A hydrogen atmosphere was substituted in the flask, and this was stirred at room temperature for 8 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (0.50 g, 67% yield) as pale red crystals. this was heated to reflux for 2 hours the crystals precipitated by the addition of water were filtered After the crystals were washed with water, they were dried under reduced pressure with heating to give crystals that this was stirred at room temperature for 8 hours this was filtered through Celite the filtrate was concentrated The residue obtained was purified by silica gel column chromatography

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

Procedure: A solution of 4-aminocyclohexanol hydrochloride (6.08 g, 0.04 mole) in water (60 ml) was brought to pH 8 with aqueous sodium bicarbonate solution. N-carbethoxy-phthalimide (8.76 g, 0.04 mole) was added followed by tetrahydrofuran (until homogenous solution was obtained). The clear solution was stirred at room temperature overnight. During this time a white solid was precipitated. The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was extracted with ethyl acetate until the solution was clear. The ethyl acetate extracts were combined, washed with water, dried (MgSO4) and concentrated to give 4-phthalimido cyclohexanol as a white solid (7.1 g). During this time a white solid was precipitated The tetrahydrofuran was removed in vacuo the remaining aqueous solution was extracted with ethyl acetate until the solution washed with water dried (MgSO4) concentrated

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

Procedure: Potassium carbonate (1.64 g, 11.9 mmol) and N-carboethoxyphthalimide (1.59 g, 7.25 mmol) were added to a solution of 4-aminocyclohexanol hydrochloride (1.0 g, 6.59 mmol) in water (15 ml) at room temperature and stirred for 30 minutes. The reaction solution was filtered and the resulting precipitate was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain trans-2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (823 mg, 51%). The reaction solution was filtered the resulting precipitate was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 2,4-dichloro-6-phenyl-pyrimidine (0.5 g, 2.22 mmol), 4-aminocyclohexanol hydrochloride (0.12 g, 1.11 mmol), triethylamine (0.67 g, 6.62 mmol) in n-butanol (10 mL) was stirred at 120° C. for 12 hours under a nitrogen atmosphere. The reaction mixture was then concentrated under vacuum, diluted with water (25 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were collected, combined, washed with water (20 mL), dried over anhydrous sodium sulphate, and concentrated under vacuum. The residue thus obtained was purified by column chromatography using ethyl acetate-petroleum ether to give the two compounds 4-(2-chloro-6-phenyl-pyrimidin-4-ylamino)-cyclohexanol and 4-(4-chloro-6-phenyl-pyrimidin-2-ylamino)-cyclohexanol in ratio 1:2 (overall yield: 63%). The reaction mixture was then concentrated under vacuum diluted with water (25 mL) extracted with ethyl acetate (3×20 mL) The organic layers were collected washed with water (20 mL) dried over anhydrous sodium sulphate concentrated under vacuum The residue thus obtained was purified by column chromatography

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

Procedure: 75.5 g (0.5 Mol) of 4-aminocyclohexanolhydrochloride and 74.0 g (0.5 Mol) of phthalic acid anhydride are mixed with 65 g (0.5 Mol) of ethyl-diisopropyl-amine and 1000 ml of toluene and boiled for 36 hours with a water separator. Then water is added, the toluene phase is separated off and the aqueous phase is extracted several times with chloroform. The organic phases are combined, dried and concentrated. The concentration residue is recrystallised from isopropanol. the toluene phase is separated off the aqueous phase is extracted several times with chloroform dried concentrated The concentration residue is recrystallised from isopropanol