Nitrogen → (2S,4R)-1-tert-butyl 2-methyl 4-(aminooxy)pyrrolidine-1,2-dicarboxylate

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Reaction Steps

To a solution of (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (4.9 g, 20.0 mmol) in CH2Cl2 (50.0 mL) was added 2-hydroxyisoindolin-1,3-dione (3.26 g, 20.0 mmol) and triphenylphosphine (7.86 g, 30.0 mmol). The resultant mixture was cooled to 0° C. and diisopropylazodicarboxylate (5.90 ml, 30.0 mmol) was slowly added drop wise under N2 atmosphere. The reaction mixture was stirred at ambient temperature for 48 h. Work-up and purification as described in Example 2A, Step 1 afforded (2S,4R)-1-tert-butyl 2-methyl 4-(1,3-dioxoisoindolin-2-yloxy)pyrrolidine-1,2-dicarboxylate as a viscous oil. The resultant oily compound was dissolved in CH2Cl2 (100 ml) and cooled to 0° C. Hydrazine hydrate (4.0 mL, 40.0 mmol) was added drop wise. The reaction mixture was stirred at ambient temperature over night. Work-up and purification as described in Example 2A, Step 2 afforded (2.8 g, 53%, over two steps) of (2S,4R)-1-tert-butyl 2-methyl 4-(aminooxy)pyrrolidine-1,2-dicarboxylate as a pale yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.42 (s, 9H) 2.13-2.29 (m, 1H) 2.34-2.48 (m, 1H) 3.48-3.68 (m, 2H) 3.72 (s, 3H) 4.23-4.30 (m, 1H) 4.30-4.49 (m, 1H). MS (ES) [M+H] calculated for C11H21N2O5, 261.14. found 261.22.

Provenance & Evidence