Procedure:  50 mL, 1-neck flask, stirbar, septum, N₂ inlet

                  Dissolved 0.818 g of I, 0.784 g og II and 1.50 mL of NMM in 20 mL of THF.  Stirred at 0 C.  Added 2.294 g of BOP.  Let stir overnight as bath warmed to rt.  After 16 h, TLC (30:70 EtOAc-hexanes, Ninhydrin) showed product spot at Rf 0.24.  The reaction mixture was poured into 1.0 M HCl and extracted with EtOAc.  The organic layer was washed with sat. aq. NaHCO₃, dried over MgSO₄, filtered and the solvent was removed by rotary evaporation.  The product was isolated by flash chromatography on silica gel using 50:50 EtOAc-hexanes as eluant.  The product was a white solid.  

 

¹H NMR (CDCl₃, 300 MHz) d 6.72 (br, NH, 1H), 5.02 (br, NH, 1H), 4.55 (m, CH, 1H), 4.19 (br, CH, 1H), 3.72 (s, CO₂CH₃, 3H), 1.85-1.22 (m, CH₂s, 6H), 1.43 (s, CO₂t-Bu, 9H), 1.35 (d, J = 7.1 Hz, Ala-CH₃, 3H), 0.86 (t, J = 6.9 Hz, CH₃, 3H). 

 

notes

 

DMF is also a good solvent for this coupling.  Triethylamine is the base first reported for use in conjunction with BOP (see a) Castro, B.; Dormoy, J.R.; Evin, G.; Selve, C. Tetrahedron Lett.  1975, 1219.  b) Castro, B.; et al.  Synthesis  1976, 751).  The reaction is generally complete in a couple of hours.  The reagent has also been used to prepare phenyl esters (see Castro, B.; Evin, G.; Selve, C.; Seyer, R.  Synthesis  1977, 413).