Hydrochloric Acid → 2-[(3,4-Difluorophenyl)formamido]acetic acid

Temperatur

0 °C

Glycine (8.26 g, 110 mmol) was dissolved in 2M NaOH (125 ml, 250 mmol). The resulting colorless solution was cooled to 0° C. and 3,4-difluorobenzoyl chloride (12 mL, 95 mmol) in 60 mL of THF was added dropwise over 10 minutes. The reaction was stirred for 1 hour at 0° C. and allowed to warm to room temperature over 2 hours. The reaction was acidified to pH 1 with concentrated HCl while cooling in an ice bath. 100 mL of EtOAc was added and the mixture was poured into a separatory funnel and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with water and brine (50 mL each), dried with sodium sulfate, filtered and concentrated in vacuo to about 30 mL whereupon a solid began to crystallize. The mixture was allowed to stand overnight. The solid residue was concentrated on a rotary evaporator to remove the remaining EtOAc and then dried in a vacuum oven at 40° C. to provide the desired product, 2-(3,4-difluorobenzamido)acetic acid as an off-white solid (20.73 grams, 96%). LCMS (+ESI) m/z 216.2 [M+H]+. 1H-NMR (CDCl3) δ 12.70 (br s, 1H), 9.00 (t, 1H), 7.90 (m, 1H), 7.75 (m, 1H), 7.55 (m, 1H), 3.90 (s, 2H).

1. temperatureto warm to room temperature over 2 hours
2. temperaturewhile cooling in an ice bath
3. additionthe mixture was poured into a separatory funnel
4. customthe layers separated
5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
6. washThe combined organic layers were washed with water and brine (50 mL each)
7. dry with materialdried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo to about 30 mL whereupon a solid
10. customto crystallize
11. waitto stand overnight
12. concentrationThe solid residue was concentrated on a rotary evaporator
13. customto remove the remaining EtOAc
14. customdried in a vacuum oven at 40° C.

ORD-Eintrag

ord-39610c35a7e249d8beca0c400b564d72

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08835422B2