BOC-TRANS-4-AMINOCYCLOHEXANOL

Step 1 tert-butyl (trans-4-hydroxycyclohexyl)carbamate A solution of trans-4-aminocyclohexanol (5 g, 33 mmol) in 1, 4-dioxane (100 mL) was cooled to 0 °C. After 15 min, sodium hydroxide (1.6 g, 40 mmol) dissolved in water (40 mL) was added and allowed to cool for an additional 15 min. Asolution of di-tert-butyl dicarbonate (7.9 g, 36 mmol) dissolved in 1, 4-dioxane (65 mL) was thenadded to the solution of aminoalcohol and allowed to stir at rt for 14 h. The reaction wasquenched by the addition of 1 M HCl (100 mL) followed by EtOAc (150 mL). The layers wereseparated and the aqueous layer was extracted further with EtOAc (2 × 150 mL). The combinedorganic layers were washed sequentially with water (100 mL), brine (100 mL), and dried(Na2SO4) before being concentrated in vacuo to give a white solid (5.3 g, 75percent). Note: Theproduct can be carried forward to the mesylation step without further purification(1R, 4R) -4-aminocyclohexan-1-ol (15.0 g, 0.13 mol) was dissolved in methylene chloride (250 mL). Then, 0 °C a solution of di-tert-butyl dicarbonate diluted in methylene chloride (100 mL) (25.6 g, 0.12 mol) and triethylamine (45.4 mL, 0.33 mol) were slowly added dropwise in succession, And the mixture was stirred at room temperature for 14 hours. Distilled water (300 mL) was added to the reaction mixture, the reaction was terminated by stirring for 10 minutes, and extracted with methylene chloride. The organic layer was washed with distilled water and saturated brine, dried over anhydrous sodium sulfate and concentrated to give the title compound im-1c-a (24.5 g, 97percent) as a pink solidTo a solution of di-tert-butyl dicarbonate (4.087 mL, 21.01 mmol) and diisopropylethylamine (2.87 mL, 17.4 mmol) in THF (60 mL) was added (1R, 4R)-4-aminocyclohexanol (2.00 g, 17.4 mmol) and was stirred at rt for 4h. The reaction was concentrated to dryness and the residue was dried under reduced pressure to yield the title compound as a white solid (3.49 g, 87.0percent yield), which was used without further purification.To a solution of 4-aminocyclohexan-1-ol (25 g, 217.06 mmol, 1.00 equiv) and di-tert-butyl dicarbonate (47.39 g, 217.14 mmol, 1.00 equiv) in toluene (250 mL) maintained under an inert atmosphere of nitrogen was added an aqueous sodium hydroxide (10.43 g, 260.77 mmol, 1.20 equiv) solution dropwise with stirring. The resulting solution was stirred overnight at room temperature. The solid was collected by filtration then dried to give 40 g (86percent) of tert-butyl N-(4-hydroxycyclohexyl)carbamate as a white solid.To a solution of (1R, 4R)-4-aminocyclohexanol (15 g, 0.13 mol) in acetonitrile (240 mL) was added in portions di-tert-butyl dicarbonate (31.2 g, 0.14 mol). Intermediate 1.ferf-butyl (frans-4-hydroxycyclohexyl)carbamateTo a solution of (1 /?, 4/?)-4-aminocyclohexanol (15 g, 0.13 mol) in acetonitrile (240 mL) was added in portions di-ie f-butyl dicarbonate (31 .2 g, 0.14 mol). The mixture was stirred overnight at room temperature. The precipitate obtained was washed with hexane/ethyl acetate (3:1 ) and hexane giving the title compound as a white solid (83percent).To a stirred mixture of (1 r, 4r)-4-aminocyclohexanol (3.0 g) and DIPEA (5.0 mL) in DCM (100 mL) was added Boc2O (6.4 mL) slowly. The reaction mixture was stirred at RT for 3 hours. The mixture was concentrated under reduced pressure to give tert-butyl ((1 r, 4r)-4- hydroxycyclohexyl)carbamate (5.7 g) as a pink solid. MS(ES) mlz 160 (M-t-Bu+H+H).To a solution of trans-4-aminohexanol (10 g, 87 mmol) and triethylamine (18 mL, 0.13 mol) in dichloromethane (44 mL), di (tert-butyl) dicarbonate (21 g, 96 mmol) was added under cooling on ice. After stirring the obtained solution at room temperature for 6.5 hours, water and 1 N hydrochloric acid were added to the reaction solution, and the obtained solution was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then concentrated under vacuum. The obtained crude product was purified by recrystallization with a mixed solvent of hexane/ethyl acetate, and the precipitated solid was recovered by filtration to obtain the title compound (13 g).

Molecular Weight:215.29
XLogP3:1.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:215.15214353
Monoisotopic Mass:215.15214353
Topological Polar Surface Area:58.6
Heavy Atom Count:15
Complexity:214
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes