tert-butyl N-[(2S)-1-cyclohexyl-3-hydroxypropan-2-yl]carbamate

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

Procedure: A mixture of tert-butyl[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]carbamate (3.3 g, 13 mmol), phthalimide (2.10 g, 14.3 mmol), triphenylphosphine (3.75 g, 14.3 mmol), diisopropyl azodicarboxylate (3.58 mL, 18.2 mmol) in tetrahydrofuran (30 mL, 400 mmol) was stirred at room temperature overnight. Direct purification by combi-flash chromatography afforded 2.8 g (56% yield) of the desired product. LC-MS found: 287.1 (M−Boc)+. Direct purification by combi-flash chromatography

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

Procedure: To a solution of (2S)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropanoic acid (5.0 g, 18 mmol) in tetrahydrofuran (50 mL) at 0° C. was added 1.0 M borane-THF complex in THF (55.3 mL, 55.3 mmol). After addition, the reaction mixture was stirred at room temperature for 3 hours, then cooled down with an ice-bath, and quenched by the slow addition of AcOH:MeOH (1:5, 40 mL). Then the mixture was warmed to room temperature for 2 hours. The THF volume was reduced by ½ and the product was partitioned between saturated aqueous NaHCO3 and DCM. The combined organic fractions were dried over Na2SO4 and concentrated under reduced pressure to give an oil residue which was used directly in the next reaction without further purification. LC-MS found: 168.1 (M−Boc)+. After addition cooled down with an ice-bath quenched by the slow addition of AcOH:MeOH (1:5, 40 mL) Then the mixture was warmed to room temperature for 2 hours the product was partitioned between saturated aqueous NaHCO3 and DCM The combined organic fractions were dried over Na2SO4 concentrated under reduced pressure to give an oil residue which was used directly in the next reaction without further purification

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

Procedure: The product from Example 15A and ethylamine were processed as described in Example 7B to provide the title compound.

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

Procedure: The title compound was prepared in analogy to (2S,3S)-3-amino-N-cyclopropyl-2-hydroxypentanamide dihydrochloride, Representative Procedure A, starting with (S)-tert-butyl 1-cyclohexyl-3-hydroxypropan-2-ylcarbamate in the second step (A2).

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

Procedure: The title compound was prepared in analogy to (2S,3S)-3-amino-N-cyclopropyl-2-hydroxypentanamide dihydrochloride, Representative Procedure A, starting with (S)-tert-butyl 1-cyclohexyl-3-hydroxypropan-2-ylcarbamate in the second step (A2).

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

Procedure: A solution of (S)—N-Boc-2-amino-3-cyclohexylpropanol (20 g, 0.078 mol) in CH2Cl2 (400 mL) and triethylamine (19.6 g, 0.195 mol) was cooled to −20° C. Methanesulfonyl chloride (19.5 g, 0.171 mol) was added with fast dropwise addition maintaining the internal temperature at −20° C. The reaction mixture was stirred at −20° C. for an additional 30 min then for 1 h at 0° C. and then quenched with ice-cold water (200 mL). The mixture was extracted with CH2Cl2 (3×100 mL), washed with water (3×50 mL), dried over Na2SO4, concentrated to give the crude (S)-2-(tert-butoxycarbonylamino)-3-cyclohexylpropyl methanesulfonate (23.3 g, 90%), which was used for the next reaction without further purification. 1H NMR (400 MHz, CDCl3): 4.93 (m, 1H), 4.60 (d, J=7.6 Hz, 1H), 3.67 (m, 2H), 3.12 (s, 3H), 1.87-1.50 (m, 5H), 1.45 (s, 9H), 1.40-0.72 (m, 8H), MS (E/Z): 336 (M+H+). for 1 h at 0° C. quenched with ice-cold water (200 mL) The mixture was extracted with CH2Cl2 (3×100 mL) washed with water (3×50 mL) dried over Na2SO4 concentrated

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

Procedure: A mixture of tert-butyl[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]carbamate (3.3 g, 13 mmol), phthalimide (2.10 g, 14.3 mmol), triphenylphosphine (3.75 g, 14.3 mmol), diisopropyl azodicarboxylate (3.58 mL, 18.2 mmol) in tetrahydrofuran (30 mL, 400 mmol) was stirred at room temperature overnight. Direct purification by combi-flash chromatography afforded 2.8 g (56% yield) of the desired product. LC-MS found: 287.1 (M−Boc)+. Direct purification by combi-flash chromatography

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

Procedure: A mixture of tert-butyl[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]carbamate (3.3 g, 13 mmol), phthalimide (2.10 g, 14.3 mmol), triphenylphosphine (3.75 g, 14.3 mmol), diisopropyl azodicarboxylate (3.58 mL, 18.2 mmol) in tetrahydrofuran (30 mL, 400 mmol) was stirred at room temperature overnight. Direct purification by combi-flash chromatography afforded 2.8 g (56% yield) of the desired product. LC-MS found: 287.1 (M−Boc)+. Direct purification by combi-flash chromatography

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

Procedure: To a solution of (2S)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropanoic acid (5.0 g, 18 mmol) in tetrahydrofuran (50 mL) at 0° C. was added 1.0 M borane-THF complex in THF (55.3 mL, 55.3 mmol). After addition, the reaction mixture was stirred at room temperature for 3 hours, then cooled down with an ice-bath, and quenched by the slow addition of AcOH:MeOH (1:5, 40 mL). Then the mixture was warmed to room temperature for 2 hours. The THF volume was reduced by ½ and the product was partitioned between saturated aqueous NaHCO3 and DCM. The combined organic fractions were dried over Na2SO4 and concentrated under reduced pressure to give an oil residue which was used directly in the next reaction without further purification. LC-MS found: 168.1 (M−Boc)+. After addition cooled down with an ice-bath quenched by the slow addition of AcOH:MeOH (1:5, 40 mL) Then the mixture was warmed to room temperature for 2 hours the product was partitioned between saturated aqueous NaHCO3 and DCM The combined organic fractions were dried over Na2SO4 concentrated under reduced pressure to give an oil residue which was used directly in the next reaction without further purification

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

Procedure: The product from Example 15A and ethylamine were processed as described in Example 7B to provide the title compound.

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

Procedure: The product from Example 15A and ethylamine were processed as described in Example 7B to provide the title compound.

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

Procedure: To a stirred solution of tert-butyl (S)-3-cyclohexyl-1-hydroxypropan-2-ylcarbamate (0.23 g, 0.9 mmol) in 1,2-dichloroethane (5 mL), was added Dess-Martin periodinane (0.49 g, 1.34 mmol). The resulting mixture was heated in a CEM microwave synthesizer at 70° C. for 3 min, diluted with ether (100 mL), and washed with 1 N NaOH (2×10 mL). The ether layer was dried over Na2SO4, and the solvent was removed in vacuo to give (S)-tert-butyl 1-cyclohexyl-3-oxopropan-2-ylcarbamate as an oil. MS ESI+ve m/z 256 (M+1). washed with 1 N NaOH (2×10 mL) The ether layer was dried over Na2SO4 the solvent was removed in vacuo