Triethylamine → HCID 18790053, compound

Temperature

0 °C

A solution containing (-)-4-benzyl-3-(4-phenylsulfonylbutanoyl)oxazolidin-2-one (2 g, 5.16 mmol) in anhydrous CH2Cl2 (20 mL) is cooled to 0° C. Di-n-butylboron triflate (1 M in CH2Cl2, 6 mL, 6.03 mmol) is added by syringe over 15 minutes followed by the addition of triethylamine (0.68 g, 6.76 mmol). The clear yellow solution is then cooled to -78° C. Freshly distilled 5-phenylpentanal (0.92 g, 5.72 mmol) in anhydrous CH2Cl2 (2 mL) is added dropwise to the reaction mixture. After 30 min, the reaction mixture is warmed to 0° C. and maintained at this temperature for 1 hour. The reaction mixture is quenched by the slow addition of 3:1 MeOH/pH 7 phosphate buffer (30 mL) followed by 2:1 MeOH/30% H2O2 (30 mL) being careful to keep the temperature below 5° C. After the addition is complete, the reaction is maintained an additional hour at 0° C. then concentrated to half-volume in vacuo. The mixture is then diluted with diethyl ether (100 mL) and water (100 mL) and the layers are separated. The organic phase is washed with 5% NaHCO3 (3×50 mL), aqueous NaHSO3 (3×50 mL), water (50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude product is combined with the crude material obtained from four additional reactions performed on identical scale and purified by silica gel chromatography (CH2Cl2 /diethyl ether, 19:1→9:1) to provide 4 g (35%) of (-)-4-benzyl-3-[3-hydroxy-7-phenyl-2-(2-phenylsulfonylethyl)-heptanoyl]-oxazolidin-2-one as a colorless, viscous oil which is homogeneous by TLC analysis [CH2Cl2 /diethyl ether, 19:1, Rf (oxazolidinone)=0.45, Rf (aldol product)=0.40]. [α]23D -20° (c 7.5, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.42-1.58 (m, 6H), 2.06 (m, 1H), 2.20 (m, 1H), 2.24 (d, J=4 Hz, 1H), 2.58 (t, J=7.5 Hz, 2H), 2.69 (dd, J=13.3, 9.9 Hz, 1H), 3.24 (m, 3H), 3.86 (m, 1H), 3.98 (quint. J=4.2 Hz, 1H), 4.16 (m, 2H), 4.65 (m, 1H), 7.18-7.52 (m, 10H), 7.59 (m, 2H), 7.68 (m, 1H), 7.90 (m, 2H) ppm. Mass spectrum (FAB) m/z 550 (M+H)+.

1. temperatureThe clear yellow solution is then cooled to -78° C
2. temperaturethe reaction mixture is warmed to 0° C.
3. temperaturemaintained at this temperature for 1 hour
4. customThe reaction mixture is quenched by the slow addition of 3:1 MeOH/pH 7 phosphate buffer (30 mL)
5. customthe temperature below 5° C
6. additionAfter the addition
7. temperaturethe reaction is maintained an additional hour at 0° C.
8. concentrationthen concentrated to half-volume in vacuo
9. additionThe mixture is then diluted with diethyl ether (100 mL) and water (100 mL)
10. customthe layers are separated
11. washThe organic phase is washed with 5% NaHCO3 (3×50 mL), aqueous NaHSO3 (3×50 mL), water (50 mL), brine (50 mL)
12. dry with materialdried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customobtained from four additional reactions
16. custompurified by silica gel chromatography (CH2Cl2 /diethyl ether, 19:1→9:1)

ORD record

ord-78231489b9374ac0bfa67c87bb4b0d54

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06057369