Hydrochloric Acid → N-Boc-O-TBDMS-D-threonine

Participants

Reaction Steps

A solution of (2R,3S)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutanoic acid (Frontier Scientific, Utah) (9.94 g, 45.3 mmol) in DCM (100 mL) was treated with 2,6-dimethylpyridine (Fluka) (15.79 mL, 136 mmol). A solution of tert-butyldimethylsilyl trifluoromethanesulfonate (Fluka) (22.9 mL, 100 mmol) in DCM (50 mL) was added dropwise over 1 h. The mixture was stirred for an additional 2 h, after which time the reaction was complete by LC-MS analysis. The mixture was diluted with saturated brine (100 mL) and acidified with a slight excess of 1.0 M aq. HCl. The mixture was stirred for 30 min, the layers were separated, and the aq. layer was extracted with DCM (100 mL). The combined organic extracts were dried (MgSO4) and concentrated to give crude product as a white semi-solid (26 g). The crude product was dissolved in MeOH (25 mL) and a solution of anhydrous Na2CO3 (4.80 g, 45.3 mmol) in water (25 mL) was added dropwise. The solution was stirred for 15 min and then concentrated to remove the MeOH. The resulting oily solution was diluted with water (175 mL) and hexane (200 mL) and stirred for 15 min. The aq. layer was separated and washed with a further 200 mL of hexane. The aq. layer was separated, diluted with DCM (200 mL), and 1.0 M aq. HCl was added dropwise to the stirred mixture. The mixture was separated and the aq. layer extracted with DCM (100 mL). The combined organic layers were dried (MgSO4) and concentrated to give (2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)butanoic acid (615a) (14.52 g, 43.5 mmol, 96% yield) as a colorless viscous oil. LC-MS m/z 356.1 [M+Na]1.

Provenance & Evidence