635319-09-4

(3R,4R)-tert-Butyl 3-Hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate has been used as a reactant for the preparation of transition state analogue inhibitors of human 5’-Methylthioadenosine phosphorylase (MTAP).

The general procedure for the synthesis of tert-butyl (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate from the compound (CAS: 635319-08-3) was as follows: to an ethanol ((S)-1,2-dihydroxyethyl)pyrrolidine (3.4 g, 13.7 mmol) solution of N-tert-butoxycarbonyl-(3R,4S)-3-hydroxy-4-[(S)-1,2-dihydroxyethyl]pyrrolidine ( 50 mL) solution of sodium periodate (3.4 g, 16 mmol) was added dropwise to an aqueous (25 mL) solution of sodium periodate (3.4 g, 16 mmol) while maintaining the reaction temperature at 0 °C. The reaction mixture was continued to be stirred at 0 °C for 20 min. Subsequently, sodium borohydride (2.0 g, excess) was added in batches to ensure that the reaction temperature was maintained at 0 °C. After completion of addition, the solids were removed by filtration and the filter cake was washed with ethanol (50 mL). The filtrates were combined and concentrated in vacuum to give a syrupy product. Purification by column chromatography gave the target product 1 (2.74 g, 92% yield) in syrupy form.

[1] Journal of Medicinal Chemistry, 2003, vol. 46, # 24, p. 5271 - 5276
[2] Patent: WO2004/18496, 2004, A1. Location in patent: Page 23-24