Benzyl Bromide → Benzyl 3-(2-hydroxy-5-(Ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoate

Participants

Reaction Steps

An aqueous KOH solution (0.14 g, 2.5 mmol) was added to a stirring solution of 121 (1.1 g, 2.5 mmol) in acetonitrile (5 mL). After 10 min the solvent was evaporated under reduced pressure and the residue was dried under vacuum for 1 hr. The pale yellow solid was resuspended in DMF (10 mL) followed by the addition of benzylbromide (330 μL, 2.8 eq). The resulting solution was stirred at room temperature for 2 hr. The mixture was diluted with EtOAC (80 mL) and washed with H2O and saturated aqueous NaCl, followed by drying over Na2SO4. The crude product was purified by silica gel chromatography (0-10% methanol in CH2Cl2) on a Biotage™ flash chromatography system, resulting in 122 as a pale yellow liquid (0.64 g, 48%): 1H NMR (400 MHz, CDCl3) δ 1.23 (t, J=7.1, 3H), 1.26 (t, J=7.1, 3H), 1.30 (t, J=7.1, 3H), 1.45 (s, 3H), 1.49 (s, 3H), 2.60 (dd, J=17.4, 20.9, 2H), 3.00 (AB q, J=14.0, 2H), 3.78-3.88 (m, 2H), 3.99-4.15 (m, 4H), 4.93 (s, 2H), 6.75-6.78 (m, 1H), 7.14 (dd, J=2.0, 7.5, 2H), 7.25-7.31 (m, 3H), 7.58 (ddd, J=1.4, 8.0, 11.9, 1H), 7.64 (d, J=13.4, 1H): 31P (162 MHz, CDCl3) δ 21.04 (d, J=4.6, 1 P), 36.00 (d, J=4.6, 1 P).

Provenance & Evidence