tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4S)-6-iodo-3,4-dihydro-2H-chromen-4-yl]amino}propylcarbamate → tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4S)-6-neopentyl-3,4-dihydro-2H-chromen-4-yl]amino}propylcarbamate

Participants

Reaction Steps

To neopentyl zinc chloride (prepared as previously described) (51 ml, 11 mmol, 0.2 M in THF) under a nitrogen atmosphere at r.t. was added tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4S)-6-iodo-3,4-dihydro-2H-chromen-4-yl]amino}propylcarbamate (1.3 g, 2.2 mmol) and Pd(dppf)Cl2 (0.09 g, 0.1 mmol) as solids. The reaction mixture was stirred at r.t. for 12 h and then heated to 50° C. for 8 h. The reaction was cooled to r.t. then quenched with 20 ml of aqueous NH4Cl and extracted with EtOAc (3×100 ml). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to yield a brown oil. The residue was dissolved in CH2Cl2 and absorbed onto 6 g of silica gel. Flash chromatography (3–5% MeOH/CHCl3 with 20 drops of NH4OH/L, Biotage 40M) yields the desired product, which is identical to the material prepared by the previously described methods.

Provenance & Evidence