Hydrochloric Acid → 4,5,6,7-Tetrahydrofuro[3,2-C]pyridine

3.7 g (46 mmole) of a 37% aqueous formaldehyde solution were added dropwise at room temperature to 5.1 g (46 mmole) of 2-furylethylamine [the compound described, for example, in Brit., J. Pharmacol., 9, 376 (1954)], and the resulting mixture was stirred for about 15 minutes, after which it was extracted with diethyl ether. The organic extract was washed with water and dried over anhydrous sodium sulfate, and then the diethyl ether was removed by distillation under reduced pressure. 5 ml of dimethylformamide were added to the residue, and the resulting solution was added dropwise to 15 ml of dimethylformamide containing 3.6 g (100 mmole) of dry hydrogen chloride at room temperature. The resulting mixture was then stirred for 3 hours. At the end of this time, the greater part of the dimethylformamide was removed by distillation under reduced pressure, and then water and a 0.1N aqueous solution of sodium hydroxide were added to the residue so as to adjust its pH to a value of about 11; the mixture was then extracted with chloroform. The organic extract was washed with water and dried over anhydrous sodium sulfate. The chloroform was then removed by evaporation under reduced pressure, and the resulting residue was purified by silica gel column chromatography, using a 50:1 by volume mixture of chloroform and methanol as the eluent, to give the title compound as a brown oil in a yield of 27%.

1. extractionafter which it was extracted with diethyl ether
2. extractionThe organic extract
3. washwas washed with water
4. dry with materialdried over anhydrous sodium sulfate
5. customthe diethyl ether was removed by distillation under reduced pressure
6. addition5 ml of dimethylformamide were added to the residue
7. stirringThe resulting mixture was then stirred for 3 hours
8. customAt the end of this time, the greater part of the dimethylformamide was removed by distillation under reduced pressure
9. additionwater and a 0.1N aqueous solution of sodium hydroxide were added to the residue so as
10. extractionthe mixture was then extracted with chloroform
11. extractionThe organic extract
12. washwas washed with water
13. dry with materialdried over anhydrous sodium sulfate
14. customThe chloroform was then removed by evaporation under reduced pressure
15. customthe resulting residue was purified by silica gel column chromatography
16. additionby volume mixture of chloroform and methanol as the eluent

ORD record

ord-4cc2addece824bd58d6e917920384de5

Source dataset

uspto-grants-1994_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05288726