Ethanol → HCID 178517339, compound

Temperature

90 °C

To an ACE sealable tube was added 3-fluorobenzene-1,2-diamine (475.99 mg, 3.77 mmol), ethanol (5 ml) and ethyl trifluoropyruvate (0.500 ml, 3.77 mmol) at rt. The tube was sealed and placed in an oil bath at 90° C. The mixture was stirred at 90° C. for 3 hr, cooled to rt and the LC/MS showed starting diamines and three new peaks. More ethyl trifluoropyruvaate (0.2 ml) was added and the mixture was stirred at 90° C. overnight. The reaction mixture was cooled to rt and LC/MS showed no diamines, and two of the three new peaks remained. The reaction mixture was concentrated to give a dark solid, diluted with dichloromethane/dimethylformamide (3/1, 60 ml) and washed with HCl (1 N, 2×20 ml) and an aquious solution of sodium thiosulfate (0.1 M, 2×20 ml). The combined aq. layers were back-extracted with dichloromethane/dimethylformamide (3/1, 2×20 ml). The combined organic layers were washed with water and concentrated to give a dark solid (1.72 g). The solid was dissolved in acetone and silica gel (46 g) was added. The mixture was dried in vacuo, loaded on a silica gel column and purified by flash chromatography (CH3CN/CHCl3=1/8, 1/6 then 1/4) to give the title compound 112a (474.9 mg, 2.046 mmol, 54.2% yield).

1. customThe tube was sealed
2. customplaced in an oil bath at 90° C
3. temperaturecooled to rt
4. additionMore ethyl trifluoropyruvaate (0.2 ml) was added
5. stirringthe mixture was stirred at 90° C. overnight
6. temperatureThe reaction mixture was cooled to rt
7. concentrationThe reaction mixture was concentrated
8. customto give a dark solid
9. washwashed with HCl (1 N, 2×20 ml)
10. extractionThe combined aq. layers were back-extracted with dichloromethane/dimethylformamide (3/1, 2×20 ml)
11. washThe combined organic layers were washed with water
12. concentrationconcentrated

ORD record

ord-785cf3d0eebf47d4a16a672351d4a849

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748374B2