Diisopropylethylamine → 3-{[2-[2,6-Bis(isopropyl)phenoxycarbonyloxy]-benzoyl]amino}-propanoic Acid

To a solution of crude compound (106) (0.4 g, 1.1 mmol) from above and beta-alanine tert-butyl ester hydrochloride (0.2 g, 1.1 mmol) in DMF (5 mL) was added diisopropylethylamine (0.41 mL, 2.3 mmol) followed by O-(benotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.44 g, 1.1 mmol). The resulting reaction mixture was stirred at room temperature for 14 h, diluted with ethyl acetate (50 mL), washed with 10% aqueous citric acid solution (30 mL), followed by saturated aqueous NaHCO3 solution (30 mL) and brine (2×20 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The crude residue was then dissolved in anhydrous dichloromethane (5 mL) and cooled to 0° C. before a solution of hydrochloric acid (1 mL, 4 N in dioxane) was added. The reaction was stirred for 2 h at 0° C. and the solvent was removed in vacuo. The crude residue was purified by preparative LC/MS to afford 50 mg (8% yield over three steps) of the title compound (103). 1H NMR (400 MHz, CDCl3): δ 7.85 (dd, J=7.6, 1.6 Hz, 1H), 7.51–7.48 (m, 1H), 7.34–7.13 (m, 5H), 3.72 (q, J=6.0 Hz, 2H), 3.13–3.10 (m, 2H), 2.67 (t, J=6.4 Hz, 2H), 1.25 (d, J=6.8 Hz, 121). MS (ESI) m/z 414.3 (M+H+).

1. customThe resulting reaction mixture
2. washwashed with 10% aqueous citric acid solution (30 mL)
3. dry with materialThe organic phase was dried over MgSO4
4. concentrationconcentrated in vacuo
5. dissolutionThe crude residue was then dissolved in anhydrous dichloromethane (5 mL)
6. temperaturecooled to 0° C. before a solution of hydrochloric acid (1 mL, 4 N in dioxane)
7. additionwas added
8. stirringThe reaction was stirred for 2 h at 0° C.
9. customthe solvent was removed in vacuo
10. customThe crude residue was purified by preparative LC/MS

ORD record

ord-959d9666dd6343b4959a95e818e02c60

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230003B2