(2R)-2-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid

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

Procedure: (R)-3-(tert-Butoxycarbonylamino)-2-methylpropanoic acid (465 mg, 2.3 mmol) was dissolved in dichloromethane (11 ml). 4-Dimethylaminopyridine (280 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (877 mg, 4.58 mmol) were added, followed by N-hydroxysuccinimide (290 mg, 2.52 mmol). After 4 h of stirring at room temperature, concentrated ammonium hydroxide (1.6 ml) was added slowly. The reaction mixture was stirred for an additional 20 min then aqueous HCl and ethyl acetate were added and the aqueous layer was extracted six times with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography to give 335 mg (72%) of ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester. (M+Na)+=225. The reaction mixture was stirred for an additional 20 min the aqueous layer was extracted six times with ethyl acetate The combined organic layers were washed with sodium bicarbonate solution dried over sodium sulfate After evaporation the residue was purified by silica gel chromatography

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

Procedure: (R)-3-(tert-Butoxycarbonylamino)-2-methylpropanoic acid (465 mg, 2.3 mmol) was dissolved in dichloromethane (11 ml). 4-Dimethylaminopyridine (280 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (877 mg, 4.58 mmol) were added, followed by N-hydroxysuccinimide (290 mg, 2.52 mmol). After 4 h of stirring at room temperature, concentrated ammonium hydroxide (1.6 ml) was added slowly. The reaction mixture was stirred for an additional 20 min then aqueous HCl and ethyl acetate were added and the aqueous layer was extracted six times with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography to give 335 mg (72%) of ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester. (M+Na)+=225. The reaction mixture was stirred for an additional 20 min the aqueous layer was extracted six times with ethyl acetate The combined organic layers were washed with sodium bicarbonate solution dried over sodium sulfate After evaporation the residue was purified by silica gel chromatography

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

Procedure: (R)-3-(tert-Butoxycarbonylamino)-2-methylpropanoic acid (465 mg, 2.3 mmol) was dissolved in dichloromethane (11 ml). 4-Dimethylaminopyridine (280 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (877 mg, 4.58 mmol) were added, followed by N-hydroxysuccinimide (290 mg, 2.52 mmol). After 4 h of stirring at room temperature, concentrated ammonium hydroxide (1.6 ml) was added slowly. The reaction mixture was stirred for an additional 20 min then aqueous HCl and ethyl acetate were added and the aqueous layer was extracted six times with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography to give 335 mg (72%) of ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester. (M+Na)+=225. The reaction mixture was stirred for an additional 20 min the aqueous layer was extracted six times with ethyl acetate The combined organic layers were washed with sodium bicarbonate solution dried over sodium sulfate After evaporation the residue was purified by silica gel chromatography

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

Procedure: To a 0° C. mixture of (2R)-3-t-butoxycarbonylamino-2-methylpropionic acid (4.6 g, 21.0 mmol) in THF (100 mL) was added 2 M Me2S.BH3/THF (16 mL, 31.5 mmol, 1.5 equivalents). After stirring for 2 h, water was added and the mixture stirred for 18 h. The mixture was diluted with CH2Cl2 and washed with satd Na2CO3. The organic layer was dried (Na2SO4), concentrated, and chromatographed (CH2Cl2; EtOAc) to give the title compound as an oil (2.4 g, 61%). the mixture stirred for 18 h washed with satd Na2CO3 The organic layer was dried (Na2SO4) concentrated chromatographed (CH2Cl2; EtOAc)

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

Procedure: (R)-3-(tert-Butoxycarbonylamino)-2-methylpropanoic acid (465 mg, 2.3 mmol) was dissolved in dichloromethane (11 ml). 4-Dimethylaminopyridine (280 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (877 mg, 4.58 mmol) were added, followed by N-hydroxysuccinimide (290 mg, 2.52 mmol). After 4 h of stirring at room temperature, concentrated ammonium hydroxide (1.6 ml) was added slowly. The reaction mixture was stirred for an additional 20 min then aqueous HCl and ethyl acetate were added and the aqueous layer was extracted six times with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography to give 335 mg (72%) of ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester. (M+Na)+=225. The reaction mixture was stirred for an additional 20 min the aqueous layer was extracted six times with ethyl acetate The combined organic layers were washed with sodium bicarbonate solution dried over sodium sulfate After evaporation the residue was purified by silica gel chromatography