Hydrochloric Acid → HCID 67009332, compound

A flask was charged with 3-benzyloxy-2-tert-butoxycarbonylaminopropionic acid (5.0 g, 16.9 mmoles), HATU (7.0 g, 18.6 mmoles) and DMF (5 mL). DIEA (8.8 mL, 50.7 mmoles) was added and the mixture was stirred for 15 minutes. 4-Phenoxyaniline (3.4 g, 18.6 mmoles) was added and the mixture was stirred at ambient temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and deionized water. The aqueous layer was separated and extracted twice with ethyl acetate. The combined extract was washed sequentially with 5% lithium chloride (3×10 mL), 1N sodium bicarbonate (2×10 mL), 5% citric acid (2×10 mL), deionized water (2×10 mL) and then brine (1×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was recrystallized from methanol to afford a white solid. The solid was combined with 4N hydrogen chloride in dioxane (25 mL). The mixture was stirred at ambient temperature for 18 hours. Volatiles then were removed under rotary evaporation. The resultant oil was partitioned between 1N sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined extract was washed with brine (2×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude was recrystallized from methanol to give 2-amino-3-benzyloxy-N-(4-phenoxyphenyl)propanamide (2 g, 5.47 mmoles, 33% yield), as an off-white solid. 1H-NMR (400 MHz, CDCl3): δ 9.55 (s, 1H), 7.60-7.50 (m, 2H), 7.40-7.27 (m, 5H), 7.08 (t, 1H), 7.01-6.95 (m, 3H), 4.57 (t, 2H), 3.85-3.70 (m, 3H), 1.97 (2, 2H). MS (D) for C22H22N2O3. found 363.0 (MH+).

1. stirringthe mixture was stirred at ambient temperature for 18 hours
2. customThe reaction mixture was partitioned between ethyl acetate
3. customThe aqueous layer was separated
4. extractionextracted twice with ethyl acetate
5. extractionThe combined extract
6. washwas washed sequentially with 5% lithium chloride (3×10 mL), 1N sodium bicarbonate (2×10 mL), 5% citric acid (2×10 mL), deionized water (2×10 mL)
7. dry with materialbrine (1×10 mL), dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude material was recrystallized from methanol
11. customto afford a white solid
12. stirringThe mixture was stirred at ambient temperature for 18 hours
13. customVolatiles then were removed under rotary evaporation
14. customThe resultant oil was partitioned between 1N sodium bicarbonate and ethyl acetate
15. extractionThe aqueous layer was extracted with ethyl acetate
16. extractionThe combined extract
17. washwas washed with brine (2×10 mL)
18. dry with materialdried over anhydrous sodium sulfate
19. filtrationfiltered
20. concentrationconcentrated in vacuo
21. customThe crude was recrystallized from methanol

ORD record

ord-91a2803a37ca40c6b2d140cdcc66bcb7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791102B2