Hydrogen Peroxide → (2R,4R)-tert-butyl 4-(allyloxy)-2-((1S,2S)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Step O (6): (2S,3S)-2-(3,5-difluorobenzyl)-3-((2R,4R)-4-(allyloxy)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-(tert-butyldimethylsilyloxy)propanoic acid. The compound of Step O (5), (2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylate, 6.5 grams, 0.011 mmol) was dissolved in 30 mL of dichloromethane and treated with 5.6 mL (32 mmol) of DIEA, followed by 3.43 g (13.0 mmol) of tert-butyldimethylsilyl triflate. After 30 min, the reaction had gone to completion by tlc analysis eluting with 2:3 ethyl acetate:hexanes and was washed twice with a satd. NaHCO3 solution and once with brine. The organic layer was dried and concentrated in vacuo to an oil. The crude product thus obtained was dissolved in 150 mL of THF and chilled to 0° C. A solution of 30% H2O2 in water (9 mL, 0.088 mmol) was then added, followed by a solution of lithium hydroxide (0.53 g, 0.022 mmol) dissolved in 40 mL of water. The reaction solution was allowed to warm to rt and stirred 16 h. The mixture was then diluted with 100 mL of ether and washed twice with a satd. NaHCO3 solution and once with brine. The organic layer was dried and concentrated to an oil which was purified by silica gel chromatography eluting with 2:3 ethyl acetate:hexanes to provide 3.77 g (62%) of the desired title compound as a white foam. 1H NMR (400 MHz, CDCl3) δ 0.07 (d, J=23.67 Hz, 6 H) 0.93 (s, 9 H) 1.35 (s, 9 H) 2.06 (m, 1 H) 2.22 (m, 1 H) 2.46 (m, 1 H) 2.78 (t, J=12.59 Hz, 1 H) 2.94 (m, 1 H) 3.08 (m, 1 H) 3.82 (m, 1 H) 3.97 (m, 4 H) 4.53 (d, J=6.80 Hz, 1 H) 5.15 (d, J=10.32 Hz, 1 H) 5.25 (dd, J=17.25, 1.13 Hz, 1 H) 5.86 (m, J=22.54, 10.70, 5.54 Hz, 1 H) 6.59 (t, J=9.06 Hz, 1 H) 6.64 (m, 1 H) 6.69 (d, J=6.55 Hz, 1 H).

Provenance & Evidence