Benzylamine → 4-(Benzylamino)-3,3-difluoro-4-oxobutanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,2-difluorosuccinic acid (2.15 g, 14.0 mmol) in iPrOAc (23 mL) was added trifluoroacetic anhydride (2.34 mL, 16.7 mmol) in one portion at ambient temperature. The reaction solution was stirred at 50° C. for 2 hr. The reaction solution was allowed to cool to 5° C. in an ice bath. Benzyl amine (2.29 mL, 20.9 mmol) was added dropwise while the reaction temperature was maintained below 20° C. The solution was stirred at ambient temperature for 2 hr. The reaction was quenched with water (10 mL) followed by saturated Na2CO3 to pH 8-9. The separated organic phase was discarded. The aqueous phase was acidified with 6 N HCl to pH 1 and extracted with EtOAc (2×100 mL). The combined organic phase was washed with 2 N HCl, brine (100 mL), dried over MgSO4 filtered and concentrated. The intermediate was carried forward without further purification (2.89 g, 56.8% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.28-7.42 (m, 5 H) 7.14-7.21 (m, 1 H) 6.77 (br. s., 1 H) 4.54 (d, J=5.87 Hz, 2 H) 3.39 (t, J=14.18 Hz, 2 H).

Provenance & Evidence