Hydrochloric Acid → HCID 59643910, compound

5-(4-Fluorophenyl)-5-oxopentanoic acid (10.08 g, 47.9 mmol) and triethylamine (6.8 mL, 4.94 g, 48.8 mmol) were dissolved in tetrahydrofuran (50 mL). The reaction was cooled to −5° C. (ice/brine bath), trimethylacetyl chloride (6.0 mL, 5.87 g, 48.7 mmol) was added quickly drop-wise and the mixture was warmed to room temperature and stirred for 1.5 h. The reaction was cooled to −5° C. (ice/brine bath) again for 30 min, filtered through Celite®, washed with cold 1:1 hexane-tetrahydrofuran (60 mL) and hexane (120 mL). The filtrate was concentrated, dissolved in N,N-dimethylformamide (16 mL) and to this mixture was added (S)-benzyl-2-oxazolidinone (8.47 g, 47.8 mmol) and 4-dimethylaminopyridine (8.57 g, 70.2 mmol) as solids. The reaction was stirred at room temperature for 20 h, poured into 1.0 N hydrochloric acid (400 mL) and extracted with ethyl acetate (2×300 mL). The organic layer was washed with water (400 mL), quarter saturated sodium bicarbonate solution (400 mL), brine (200 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by crystallization from hot isopropyl alcohol (75 mL) with slow cooling to room temperature over 16 h. The crystals were filtered cold and washed with cold isopropyl alcohol (50 mL) to afford (4S)-4-benzyl-3-[5-(4-fluorophenyl)-5-oxopentanoyl]-1,3-oxazolidin-2-one (13.87 g, 78% yield) as a white crystalline solid; mp 114.5° C.; Rf 0.29 (1:2 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 8.03-7.98 (m, 2H), 7.37-7.19 (m, 5H), 7.14 (t, J=8.7 Hz, 2H), 4.72-4.64 (m, 1H), 4.25-4.15 (m, 2H), 3.32 (dd, J=13.3, 3.4 Hz, 1H), 3.12-3.01 (m, 4H), 2.78 (dd, J=13.3, 9.6 Hz, 1H), 2.15 (quint., J=7.2 Hz, 2H) ppm.

1. additionwas added quickly drop-wise
2. filtrationfiltered through Celite®
3. washwashed with cold 1:1 hexane-tetrahydrofuran (60 mL) and hexane (120 mL)
4. concentrationThe filtrate was concentrated
5. dissolutiondissolved in N,N-dimethylformamide (16 mL) and to this mixture
6. stirringThe reaction was stirred at room temperature for 20 h
7. extractionextracted with ethyl acetate (2×300 mL)
8. washThe organic layer was washed with water (400 mL), quarter saturated sodium bicarbonate solution (400 mL), brine (200 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by crystallization from hot isopropyl alcohol (75 mL)
13. temperaturewith slow cooling to room temperature over 16 h
14. filtrationThe crystals were filtered cold
15. washwashed with cold isopropyl alcohol (50 mL)

ORD record

ord-f0bcdc9c55894effb4b553d16e2cbcec

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07320972B2