1-(cyclohexylamino)propan-2-ol

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

Procedure: To a stirred solution of 1-(cyclohexylamino)-propan-2-ol (crude 2.6 g) in DCE (30 mL) were added successively HCHO (35% in water, 2.1 mL, 24.8 mmol), Na(OAc)3BH (10.5 g, 49.6 mmol) and acetic acid (1 mL) at ice-cold conditions. The resulting mixture was allowed to stir at rt for 16 hours. The reaction was diluted with ethyl acetate and basified with 1N NaOH. The organic layer was separated, washed with water and brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 5% MeOH/DCM to provide 1-(cyclohexyl(methyl)amino)propan-2-ol. Yield: 1.0 g The organic layer was separated washed with water and brine dried over Na2SO4 filtered concentrated The crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 5% MeOH/DCM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-amino-2-propanol (1.0 mL, 13.31 mmol) in ethanol (15 mL) was added cyclohexanone (1.9 g, 19.9 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then NaBH4 (0.725 g, 19.17 mmol) was added. The reaction mixture was stirred at rt for 15 minutes and then quenched with water. The reaction mixture was filtered through a Celite® pad and the filtrate was concentrated. The residue was dissolved in DCM, dried over Na2SO4, filtered and concentrated to provide 1-(cyclohexylamino)propan-2-ol. Yield: 2.6 g (crude). 1H NMR (DMSO-d6) δ 4.39-4.36 (m, 1H), 3.61-3.57 (m, 1H), 2.47-2.30 (m, 3H), 1.78-1.75 (m, 2H), 1.66-1.63 (m, 2H), 1.55-1.52 (m, 1H), 1.23-1.12 (m, 3H), 1.03-0.89 (m, 5H). 1-(cyclohexylamino)propan-2-ol may also be prepared by following procedure of Example 1. The reaction mixture was stirred at rt for 15 minutes quenched with water The reaction mixture was filtered through a Celite® pad the filtrate was concentrated The residue was dissolved in DCM dried over Na2SO4 filtered concentrated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-amino-2-propanol (15 g, 0.199 mol) in ethanol (300 ml) was added cyclohexanone (31.4 mL, 0.299 mol). The reaction mixture was stirred at 0-10° C. for 10 minutes. Sodium borohydride (10.8 g, 0.285 mol) was added at 0° C., then stirred at rt for 15 minutes. The resultant reaction mixture was quenched with water, filtered through the Celite® reagent, and solvent was evaporated. The residue was dissolved in 2N HCl, washed with ethyl acetate; the pH of the aqueous layer was adjusted to 8 using saturated sodium bicarbonate solution. The compound was extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated to dryness, and the crude material was subjected to column chromatography to obtain 1-(cyclohexylamino)propan-2-ol. Yield: 22 g (70.1%); 1H NMR (400 MHz, DMSO-d6) δ 8.25 (bs, 1H), 5.25 (bs, 1H), 3.95-3.91 (m, 1H), 2.89-2.88 (dd, J=6, 9 Hz, 2H), 2.71-2.66 (m, 1H), 2.00-1.99 (m, 2H), 1.75-1.72 (m, 2H), 1.60-1.57 (m, 1H), 1.36-0.93 (m, 8H). stirred at rt for 15 minutes The resultant reaction mixture was quenched with water filtered through the Celite® reagent, and solvent was evaporated The residue was dissolved in 2N HCl washed with ethyl acetate The compound was extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated to dryness

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-amino-2-propanol (15 g, 0.199 mol) in ethanol (300 ml) was added cyclohexanone (31.4 mL, 0.299 mol). The reaction mixture was stirred at 0-10° C. for 10 minutes. Sodium borohydride (10.8 g, 0.285 mol) was added at 0° C., then stirred at rt for 15 minutes. The resultant reaction mixture was quenched with water, filtered through the Celite® reagent, and solvent was evaporated. The residue was dissolved in 2N HCl, washed with ethyl acetate; the pH of the aqueous layer was adjusted to 8 using saturated sodium bicarbonate solution. The compound was extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated to dryness, and the crude material was subjected to column chromatography to obtain 1-(cyclohexylamino)propan-2-ol. Yield: 22 g (70.1%); 1H NMR (400 MHz, DMSO-d6) δ 8.25 (bs, 1H), 5.25 (bs, 1H), 3.95-3.91 (m, 1H), 2.89-2.88 (dd, J=6, 9 Hz, 2H), 2.71-2.66 (m, 1H), 2.00-1.99 (m, 2H), 1.75-1.72 (m, 2H), 1.60-1.57 (m, 1H), 1.36-0.93 (m, 8H). stirred at rt for 15 minutes The resultant reaction mixture was quenched with water filtered through the Celite® reagent, and solvent was evaporated The residue was dissolved in 2N HCl washed with ethyl acetate The compound was extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated to dryness

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

Procedure: To a stirred solution of 1-(cyclohexylamino)-propan-2-ol (crude 2.6 g) in DCE (30 mL) were added successively HCHO (35% in water, 2.1 mL, 24.8 mmol), Na(OAc)3BH (10.5 g, 49.6 mmol) and acetic acid (1 mL) at ice-cold conditions. The resulting mixture was allowed to stir at rt for 16 hours. The reaction was diluted with ethyl acetate and basified with 1N NaOH. The organic layer was separated, washed with water and brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 5% MeOH/DCM to provide 1-(cyclohexyl(methyl)amino)propan-2-ol. Yield: 1.0 g 1H NMR (DMSO-d6) δ 4.11 (brs, 1 H), 3.65-3.57 (m, 1 H), 2.35-2.20 (m, 3 H), 2.19 (s, 3 H), 1.72-1.68 (m, 4 H), 1.57-1.54 (m, 1 H), 1.24-1.05 (m, 5 H), 1.01 (d, J=6 Hz, 3 H). The organic layer was separated washed with water and brine dried over Na2SO4 filtered concentrated The crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 5% MeOH/DCM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-amino-2-propanol (1.0 mL, 13.31 mmol) in ethanol (15 mL) was added cyclohexanone (1.9 g, 19.9 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then NaBH4 (0.725 g, 19.17 mmol) was added. The reaction mixture was stirred at rt for 15 minutes and then quenched with water. The reaction mixture was filtered through a Celite® pad and the filtrate was concentrated. The residue was dissolved in DCM, dried over Na2SO4, filtered and concentrated to provide 1-(cyclohexylamino)propan-2-ol. Yield: 2.6 g (crude). 1H NMR (DMSO-d6) δ 4.39-4.36 (m, 1 H), 3.61-3.57 (m, 1 H), 2.47-2.30 (m, 3 H), 1.78-1.75 (m, 2 H), 1.66-1.63 (m, 2 H), 1.55-1.52 (m, 1 H), 1.23-1.12 (m, 3 H), 1.03-0.89 (m, 5 H). 1-(cyclohexylamino)propan-2-ol may also be prepared by following procedure of Example 1. The reaction mixture was stirred at rt for 15 minutes quenched with water The reaction mixture was filtered through a Celite® pad the filtrate was concentrated The residue was dissolved in DCM dried over Na2SO4 filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-amino-2-propanol (1.0 mL, 13.31 mmol) in ethanol (15 mL) was added cyclohexanone (1.9 g, 19.9 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then NaBH4 (0.725 g, 19.17 mmol) was added. The reaction mixture was stirred at rt for 15 minutes and then quenched with water. The reaction mixture was filtered through a Celite® pad and the filtrate was concentrated. The residue was dissolved in DCM, dried over Na2SO4, filtered and concentrated to provide 1-(cyclohexylamino)propan-2-ol. Yield: 2.6 g (crude). 1H NMR (DMSO-d6) δ 4.39-4.36 (m, 1 H), 3.61-3.57 (m, 1 H), 2.47-2.30 (m, 3 H), 1.78-1.75 (m, 2 H), 1.66-1.63 (m, 2 H), 1.55-1.52 (m, 1 H), 1.23-1.12 (m, 3 H), 1.03-0.89 (m, 5 H). 1-(cyclohexylamino)propan-2-ol may also be prepared by following procedure of Example 1. The reaction mixture was stirred at rt for 15 minutes quenched with water The reaction mixture was filtered through a Celite® pad the filtrate was concentrated The residue was dissolved in DCM dried over Na2SO4 filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-amino-2-propanol (1.0 mL, 13.31 mmol) in ethanol (15 mL) was added cyclohexanone (1.9 g, 19.9 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then NaBH4 (0.725 g, 19.17 mmol) was added. The reaction mixture was stirred at rt for 15 minutes and then quenched with water. The reaction mixture was filtered through a Celite® pad and the filtrate was concentrated. The residue was dissolved in DCM, dried over Na2SO4, filtered and concentrated to provide 1-(cyclohexylamino)propan-2-ol. Yield: 2.6 g (crude). 1H NMR (DMSO-d6) δ 4.39-4.36 (m, 1 H), 3.61-3.57 (m, 1 H), 2.47-2.30 (m, 3 H), 1.78-1.75 (m, 2 H), 1.66-1.63 (m, 2 H), 1.55-1.52 (m, 1 H), 1.23-1.12 (m, 3 H), 1.03-0.89 (m, 5 H). 1-(cyclohexylamino)propan-2-ol may also be prepared by following procedure of Example 1. The reaction mixture was stirred at rt for 15 minutes quenched with water The reaction mixture was filtered through a Celite® pad the filtrate was concentrated The residue was dissolved in DCM dried over Na2SO4 filtered concentrated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-amino-2-propanol (15 g, 0.199 mol) in ethanol (300 ml) was added cyclohexanone (31.4 mL, 0.299 mol). The reaction mixture was stirred at 0-10° C. for 10 minutes. Sodium borohydride (10.8 g, 0.285 mol) was added at 0° C., then stirred at rt for 15 minutes. The resultant reaction mixture was quenched with water, filtered through the Celite® reagent, and solvent was evaporated. The residue was dissolved in 2N HCl, washed with ethyl acetate; the pH of the aqueous layer was adjusted to 8 using saturated sodium bicarbonate solution. The compound was extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated to dryness, and the crude material was subjected to column chromatography to obtain 1-(cyclohexylamino)propan-2-ol. Yield: 22 g (70.1%); 1H NMR (400 MHz, DMSO-d6) δ 8.25 (bs, 1 H), 5.25 (bs, 1 H), 3.95-3.91 (m, 1 H), 2.89-2.88 (dd, J=6, 9 Hz, 2 H), 2.71-2.66 (m, 1 H), 2.00-1.99 (m, 2 H), 1.75-1.72 (m, 2 H), 1.60-1.57 (m, 1 H), 1.36-0.93 (m, 8 H). stirred at rt for 15 minutes The resultant reaction mixture was quenched with water filtered through the Celite® reagent, and solvent was evaporated The residue was dissolved in 2N HCl washed with ethyl acetate The compound was extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated to dryness

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-amino-2-propanol (15 g, 0.199 mol) in ethanol (300 ml) was added cyclohexanone (31.4 mL, 0.299 mol). The reaction mixture was stirred at 0-10° C. for 10 minutes. Sodium borohydride (10.8 g, 0.285 mol) was added at 0° C., then stirred at rt for 15 minutes. The resultant reaction mixture was quenched with water, filtered through the Celite® reagent, and solvent was evaporated. The residue was dissolved in 2N HCl, washed with ethyl acetate; the pH of the aqueous layer was adjusted to 8 using saturated sodium bicarbonate solution. The compound was extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated to dryness, and the crude material was subjected to column chromatography to obtain 1-(cyclohexylamino)propan-2-ol. Yield: 22 g (70.1%); 1H NMR (400 MHz, DMSO-d6) δ 8.25 (bs, 1 H), 5.25 (bs, 1 H), 3.95-3.91 (m, 1 H), 2.89-2.88 (dd, J=6, 9 Hz, 2 H), 2.71-2.66 (m, 1 H), 2.00-1.99 (m, 2 H), 1.75-1.72 (m, 2 H), 1.60-1.57 (m, 1 H), 1.36-0.93 (m, 8 H). stirred at rt for 15 minutes The resultant reaction mixture was quenched with water filtered through the Celite® reagent, and solvent was evaporated The residue was dissolved in 2N HCl washed with ethyl acetate The compound was extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated to dryness

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-amino-2-propanol (15 g, 0.199 mol) in ethanol (300 ml) was added cyclohexanone (31.4 mL, 0.299 mol). The reaction mixture was stirred at 0-10° C. for 10 minutes. Sodium borohydride (10.8 g, 0.285 mol) was added at 0° C., then stirred at rt for 15 minutes. The resultant reaction mixture was quenched with water, filtered through the Celite® reagent, and solvent was evaporated. The residue was dissolved in 2N HCl, washed with ethyl acetate; the pH of the aqueous layer was adjusted to 8 using saturated sodium bicarbonate solution. The compound was extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated to dryness, and the crude material was subjected to column chromatography to obtain 1-(cyclohexylamino)propan-2-ol. Yield: 22 g (70.1%); 1H NMR (400 MHz, DMSO-d6) δ 8.25 (bs, 1 H), 5.25 (bs, 1 H), 3.95-3.91 (m, 1 H), 2.89-2.88 (dd, J=6, 9 Hz, 2 H), 2.71-2.66 (m, 1 H), 2.00-1.99 (m, 2 H), 1.75-1.72 (m, 2 H), 1.60-1.57 (m, 1 H), 1.36-0.93 (m, 8 H). stirred at rt for 15 minutes The resultant reaction mixture was quenched with water filtered through the Celite® reagent, and solvent was evaporated The residue was dissolved in 2N HCl washed with ethyl acetate The compound was extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated to dryness

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

Procedure: Cyclohexanone (0.98 g, 10 mmol) and 1-amino-propan-2-ol (0.75 g, 10 mmol) were mixed and MeOH (20 mL), acetic acid (12 mg, 0.5 mmol), cyanoborohydride resin (7 g, 14 mmol, 2 mmol/g, prepared as described by A. R. Sande et al, Tetrahedron Letters 1984, 3501) were added. The reaction mixture was heated under reflux for 16 h. The resin was filtered off and the filtrate was evaporated in vacuo. The crude product was used without further purification. Sande et al, Tetrahedron Letters 1984, 3501) were added The reaction mixture was heated under reflux for 16 h The resin was filtered off the filtrate was evaporated in vacuo The crude product was used without further purification