Dichloromethane → L-Proline, N-(methoxycarbonyl)-L-valyl-4-hydroxy-, methyl ester, (4R)-

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Reaction Steps

In a 500 mL round-bottomed flask, (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (2.90 g, 16.6 mmol) and HATU (6.29 g, 16.6 mmol) were combined with CH2Cl2 (300 ml) to give a colorless suspension. TEA (5.03 g, 6.92 ml, 49.7 mmol) was added and stirred at rt for 30 min. (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate HCl (3.01 g, 16.6 mmol) was added and stirred at room temperature for 5 hr. It was diluted with NaHCO3 (sat. solution, 100 ml) and organic phase was separated. The aqueous layer was extracted with CH2Cl2 (2×100 ml) and the organic layer was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by a silica gel column (CH2Cl2, 20%, 40%, 60%, 80% EtOAc/CH2Cl2) to afford (2S,4R)-methyl 4-hydroxy-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-carboxylate as an oil (4.0 g, 79.9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.88 (dd, J=17.32, 6.78 Hz, 17H) 1.75-1.96 (m, 5H) 2.10 (br. s., 3H) 3.46-3.62 (m, 16H) 3.63-3.77 (m, 5H) 4.33 (d, J=8.03 Hz, 5H) 5.21 (d, J=3.76 Hz, 3H) 7.30 (d, J=8.78 Hz, 2H)

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