O-Xylene → HCID 11565355, compound

A dried, 200 mL, 3-necked, round-bottomed flask was equipped with a Teflon-coated magnetic bar and a vacuum jacketed Dean-Stark trap which was topped with a reflux condenser fitted with a Nitrogen inlet. The reaction vessel was charged with N-isopropyl-N-phenylamine (8.11 g, 60 mmol), boric acid (0.93 g, 15 mmol,), and xylene (88 mL). To the stirred reaction mixture was added 7-ethoxy-7-oxoheptanoic acid (11.29 g, 60 mmol) in one portion. The reaction was heated to reflux using a heating mantle. The azeotroped water began to separate and was collected in the Dean-Stark trap. After 16 hours of reflux, water was collected, and the reaction was allowed to cool to ambient temperature reaction. The reaction mixture was diluted with ethyl acetate (100 mL), and was washed with an aqueous 2N solution of HCl (50 mL), and followed with a saturated solution of sodium bicarbonate (60 mL). The majority of the organic solvent was removed in vacuum. To residue was added a 2 N aqueous solution of sodium hydroxide (60 mL). The mixture was heated at 60° C. for 4 hours. Upon cooling to room temperature, the mixture was washed 60 mL of ethyl acetate. After being carefully separated from the organic layer, the aqueous phase was subjected to evaporation to remove any residual ethyl acetate. Ice was added to the aqueous solution, followed by an aqueous solution of HCl (2N, 60 mL) leading to the precipitation of a white solid. Stirring was continued for an additional 30 minutes before the precipitate was collected with a sintered funnel. The collected white solid was successfully washed with water and hexane before it was in vacuo at room temperature for 12 h to afford 7.49 g (45%) of 7-[isopropyl(phenyl)amino]-7-oxoheptanoic acid as a white solid. HPLC: single peak at 4.83 min.; Mp: 62-63° C. 1H NMR (DMSO-d6,) δ: 0.95-0.97 (d, 6H), 1.08-1.10 (m, 2H), 1.34-1.40 (m, 4H), 1.76-1.79 (m, 2H), 2.09-2.13 (m, 2H), 4.81-4.85 (m, 1H), 7.18-7.20 (m, 2H), 7.44-7.46 (m, 3H). Mass (M+1): 278. Anal. Calc'd for C16H23NO3: C, 69.29; H, 8.36; N5.05. Found: C, 69.06; H, 8.45; N, 4.99.

1. customA dried, 200 mL, 3-necked, round-bottomed flask was equipped with a Teflon-coated magnetic bar
2. customwas topped with a reflux condenser
3. customfitted with a Nitrogen inlet
4. customTo the stirred reaction mixture
5. temperatureThe reaction was heated
6. temperatureto reflux
7. customto separate
8. customwas collected in the Dean-Stark trap
9. temperatureAfter 16 hours of reflux
10. customwater was collected
11. customreaction
12. washwas washed with an aqueous 2N solution of HCl (50 mL)
13. customThe majority of the organic solvent was removed in vacuum
14. additionTo residue was added a 2 N aqueous solution of sodium hydroxide (60 mL)
15. temperatureThe mixture was heated at 60° C. for 4 hours
16. temperatureUpon cooling to room temperature
17. washthe mixture was washed 60 mL of ethyl acetate
18. customAfter being carefully separated from the organic layer
19. customthe aqueous phase was subjected to evaporation
20. customto remove any residual ethyl acetate
21. additionIce was added to the aqueous solution
22. customleading to the precipitation of a white solid
23. customwas collected with a sintered funnel
24. washThe collected white solid was successfully washed with water and hexane before it
25. waitwas in vacuo at room temperature for 12 h

ORD record

ord-2a0116098a6648ada8e1993779a9cbe5

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273794B2