Synthesis
1. tert-Butyl (2R)-2-formylpyrrolidine-1-carboxylate (15.9 g, 37.4 mmol) was added in batches to a stirring solution of tert-Butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (5.0 g, 24.9 mmol) in dichloromethane (75 mL) under nitrogen protection over a 5-minute dosing period. 2. The reaction mixture was stirred for 1 hr. to form a suspension.3. The suspension was filtered through a diatomaceous earth pad and the filter cake was washed with dichloromethane (100 mL).4. The filtrate was concentrated under pressure to give the crude product.5. The crude product was purified by neutral silica gel column chromatography to give BOC-D-prolinyl aldehyde (4.4 g, 89% yield) using 12% ethyl acetate/hexanes as eluent.
References
[1] Patent: WO2015/120390, 2015, A1. Location in patent: Page/Page column 97; 178
[2] Tetrahedron Letters, 1997, vol. 38, # 37, p. 6479 - 6482
[3] Patent: WO2015/118342, 2015, A1. Location in patent: Page/Page column 94; 95
[4] Journal of Medicinal Chemistry, 1990, vol. 33, # 12, p. 3190 - 3198
[5] Tetrahedron Letters, 1990, vol. 31, # 28, p. 3957 - 3960
