Sodium hydride → HCID 86740666, compound

A solution of 2-phenyl-3-(3,4-dimethoxyphenylethyl)-5-(hydroxymethyl)oxazolidine 1 (25.76 g, 0.075 m) in pyridine (30 mL) was cooled to 10° C. and p-toluenesulfonyl chloride (14.30 g, 0.075 m) was added over 30 minutes, keeping the temperature below 25° C. After stirring at 25° C. for 3 hours, a cold solution of K2CO3 (10.37 g, 0.075 m) in H2O (70 mL) was added and the mixture was extracted with CHCl3 (3×125 mL). The extracts were washed with H2O, dried and concentrated under reduced pressure below 50° C., initially using water aspiration and finally high vacuum to yield the tosylate 2 (35.83 g, 96%). Sodium hydride (3.36 g, 0.070 m, 50% dispersion in mineral oil) was added to a solution of p-(2-oxazolyl) phenol 3 (11.29 g, 0.070 m) prepared according to the procedure of H. Jones, et al. [J. Med. Chem., 21, 1100 (1978)] in dimethylformamide (125 mL) under nitrogen and the mixture was heated at 60° C. for 30 min. A solution of the tosylate 2 (35.83 g., 0.072 m) in dimethylformamide (110 mL) was added and the mixture was refluxed for 16 hours. The solvent was removed under reduced pressure, saturated Na2CO3 solution (210 mL) added and the mixture extracted with ethyl acetate (2×250 mL) and CHCl3 (2×250 mL). The combined organic layers were dried and concentrated under reduced pressure. The residue was heated on a steam bath for 1.5 hours with 1.5N HCl (685 mL), the resulting solution cooled, and extracted with ether (2×300 mL). The acid layer was rendered alkaline with 20% NaOH solution and extracted with CHCl3 (3×500 mL). The solvent was concentrated under reduced pressure and the residue was chromatographed on silica gel and eluted with 5% MeOH--CHCl3 saturated with NH3. The product was crystallized from acetonitrile to yield 4 (7.0 g, 25%, m.p. 122°-3° C.).

1. customprepared
2. temperaturethe mixture was refluxed for 16 hours
3. customThe solvent was removed under reduced pressure, saturated Na2CO3 solution (210 mL)
4. additionadded
5. extractionthe mixture extracted with ethyl acetate (2×250 mL) and CHCl3 (2×250 mL)
6. customThe combined organic layers were dried
7. concentrationconcentrated under reduced pressure
8. temperatureThe residue was heated on a steam bath for 1.5 hours with 1.5N HCl (685 mL)
9. temperaturethe resulting solution cooled
10. extractionextracted with ether (2×300 mL)
11. extractionextracted with CHCl3 (3×500 mL)
12. concentrationThe solvent was concentrated under reduced pressure
13. customthe residue was chromatographed on silica gel
14. washeluted with 5% MeOH
15. customThe product was crystallized from acetonitrile

ORD record

ord-75344366098f4203bddbcc720a53f014

Source dataset

uspto-grants-1988_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04735961