Sodium Thiosulfate → (1R,3S,5R)-tert-butyl 3-formyl-2-azabicyclo[3.1.0]hexane-2-carboxylate

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Reaction Steps

To a solution of (1R,3S,5R)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (4.85 g, 22.74 mmol) in DCM (125 mL) at 0° C. was added Dess-Martin periodinane (11.57 g, 27.3 mmol). The reaction was warmed up to RT and stirred for 3 h. The reaction was poured into a saturated aq solution of NaHCO3 then ca ˜20 g of Na2S2O3 was added and stirred for 1 h. The layers were separated and the aqueous layer was extracted several times with DCM. The combined organic extracts were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash column chromatography (BIOTAGE®), eluting with a gradient of 0 to 40% EtOAc/hexanes to afford (1R,3S,5R)-tert-butyl 3-formyl-2-azabicyclo[3.1.0]hexane-2-carboxylate (4.47 g, 21.2 mmol, 93% yield) as colorless oil. LC-MS retention time 0.813 min; m/z no ionization (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% TFA and Solvent B was 10% H2O/90% MeOH/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, chloroform-d) δ ppm 9.48 (br s, 1H), 3.67-3.97 (m, 1H), 3.33-3.59 (m, 1H), 2.10-2.31 (m, 2H), 1.56-1.67 (m, 1H), 1.47 (br s, 9H), 0.80 (br s, 1H), 0.55 (br s, 1H).

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