(2S,3S,5S)-2-(2,6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-(tert-butoxycarbonyl)amino-1,6-diphenylhexane

13335-71-2

144163-85-9

192725-45-4

Example 18. Preparation of (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(tert-butoxycarbonyl)amino-1,6-diphenylhexane: tert-butyl (1S,3S,4S)-1 -benzyl-4-amino-3- hydroxy-5-phenylpentylcarbamate (38.5 mg, 0.1 mmol), 2, 6-dimethylphenoxyacetic acid (18.9 mg, 1.05 eq.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (29.7 mg, 1.5 eq.) and 1-hydroxybenzotriazole (20.4 mg, 1.5 eq.) were dissolved in N,N-dimethylformamide (1 mL) and stirred for 4 min. Subsequently, N-methylmorpholine (27.5 μL, 2.5 eq.) was added to the reaction mixture and stirring was continued for 16 hours. After completion of the reaction, the reaction was quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with 10% citric acid solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (3% methanol/dichloromethane) afforded a white solid product (240 mg, 76.7% yield).1H NMR (300 MHz, DMSO-D6) δ ppm: 1.31 (s, 9H), 1.39-1.55 (m, 2H), 2.14 (s, 6H), 2.61 (d, J = 6.99 Hz, 2H), 2.80 (d, J = 7.35 Hz, 2H), 3.61-3.70 (m, 1H), 3.84 (m, 1H), 4.00-4.11 (m, 2H), 4.20-4.38 (m, 1H), 4.99 (d, 1H), 6.66 (d, J = 9.19 Hz, 1H), 6.88-7.28 (m, 13H), 7.43 (d, J = 9.19 Hz, 13H), 7.43 (d, J = 9.19 Hz, 13H), 7.43 (d, J = 9.19 Hz, 13H), 7.43 (d, J = 6.99 Hz, 13H) 7.43 (d, J = 9.56 Hz, 1H); MS m/z 547.4 (M + H)+.