Triethylamine → N-({4-[(2R,3R)-3-{[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-methyl-D-valine

To a solution of N-[(4-{(2R,3R)-1-(4-fluorophenyl)-3-[(3-nitropyridin-2-yl)dithio]-4-oxoazetidin-2-yl}phenoxy)acetyl]glycyl-3-methyl-D-valine (0.030 g, 0.045 mmol) in acetone/water (2/0.5 ml) was added triphenylphosphine (0.012 g, 0.045 mmol). After 30 minutes the solvent was evaporated and to the residue was added dichloromethane (2 ml) and triethylamine (0.018 g, 0.179 mmol) followed by the addition of 2-bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethanone (0.029 g, 0.112 mmol). After 10 minutes the reaction was quenched by the addition of water (1 ml) followed by concentration of the mixture. MeOH (2 ml) was added followed by the addition of sodium borohydride (0.017 g, 0.447 mmol). Full conversion to the corresponding alcohol was achieved within 5 minutes. The reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml). Preparative HPLC of the mixture using an eluent of 20-45% CH3CN in 0.1M NH4OAc buffer followed by freeze drying of pure fractions afforded the desired compound. m/z: 694.7 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 0.89 (s, 9H), 2.78-2.89 (m, 2H), 3.82 (d, 2H), 4.05-4.28 (m, 6H), 4.51 (s, 2H), 4.55-4.61 (m, 1H), 5.01-5.03 (m, 1H), 6.72-7.37 (m, 11H), 7.81-7.87 (m, 1H), 8.25 (t, 1H).

1. customAfter 30 minutes the solvent was evaporated and to the residue
2. customAfter 10 minutes the reaction was quenched by the addition of water (1 ml)
3. additionMeOH (2 ml) was added
4. customThe reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml)
5. customdrying of pure fractions

ORD-Eintrag

ord-22d0db401233491b897fb65be36fddd8

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07906502B2