Hydrochloric Acid → 2-(Phenylamino)propanoic acid

Temperature

100 °C

A mixture of alanine (356 mg, 4.0 mmol), iodobenzene (816 mg, 4.0 mmol), trans-dichlorobis(tri-o-tolylphosphine) palladium (II) {Pd[P(o-Tol)3]2Cl2} (160 mg, 0.2 mmol), copper (I) iodide (40 mg, 0.2 mmol), K2CO3 (552 mg, 4.0 mmol), benzyltriethylammonium chloride (160 mg, 0.8 mmol), triethylamine (1.6 mL) and water (0.8 mL) in DMF (8 mL) was stirred under nitrogen atmosphere at 100° C. for 20 hours. The mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and water (50 mL), acidified with 6N HCl to the pH=2 to 3. The aqueous layer was extracted with ethyl acetate (50 mL×4). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give a red oil. Flash chromatography using hexane/ethyl acetate/acetic acid (95/5/0.5 to 80/20/0.5) to afford 300 mg (45% yield) of the title compound as a pink solid. 1H-NMR (500 MHz, CDCl3/CD3OD=0.5 ml/3 drops): δ 1.45 (d, 3H), 4.02-4.15 (m, H), 6.57-6.70 (m, 3H), 7.11-7.25 (m, 2H); Analytical HPLC: 6.10 min. LC-MS: m/e=166 (M+H+).

1. temperatureThe mixture was cooled to room temperature
2. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×4)
3. washThe combined organic layers were washed with water, brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. customevaporated in vacuo
7. customto give a red oil

ORD record

ord-f45127ea26504cf6bd066ad965ef93ee

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06531474B1