1-Butanol → 2,5-Furandione, 3-(bromomethyl)-

2-(Bromomethyl)-maleic anhydride (2) is prepared from compound 1 according to the method of Laursen et al. (1971) J. Med. Chem. 14:619-621 with the modification by Greenlee and Woodward (1980) Tetrahedron 36:3367-3375. This material (2 g) is hydrolyzed in water (20 mL) for about 1 hour at room temperature to 2-(bromomethyl)-maleic acid (3) and the solution is neutralized with 1 N NaOH (21.2 mL), degassed and kept under N2. The solution is added to a previously prepared solution of 4-aminothiophenol (1.51 g) that has been dissolved in degassed 1 N NaOH (11.6 mL) with gentle heating under N2 and filtered to remove the insoluble dimer. The filtrate is diluted with degassed water (12 mL) before being added to the above solution of compound 3. The final reaction solution is brought to about pH 11.0 with 1N NaOH and stirred under N2 at room temperature overnight. The solution is then filtered to remove small amounts of bis-(4-aminophenyl)-disulfide, cooled on ice, and acidified with 1N HCl, which gives a yellow precipitate. n-Butanol is added (40 mL) and the mixture is vigorously stirred on ice for 5 minutes. This removes the fumaric acid analog of compound 4. The solid is then collected by filtration, washed successively with 0.1 N HCl and water, and finally dried in a vacuum desiccator over P2O5, to yield the neutral compound 4.

1. customdegassed
2. additionThe solution is added to a previously prepared solution of 4-aminothiophenol (1.51 g) that
3. dissolutionhas been dissolved in degassed 1 N NaOH (11.6 mL)
4. temperaturewith gentle heating under N2
5. filtrationfiltered
6. customto remove the insoluble dimer
7. additionThe filtrate is diluted with degassed water (12 mL)
8. additionbefore being added to the above solution of compound 3
9. customThe final reaction solution
10. filtrationThe solution is then filtered
11. customto remove small amounts of bis-(4-aminophenyl)-disulfide
12. temperaturecooled on ice
13. customgives a yellow precipitate
14. stirringthe mixture is vigorously stirred on ice for 5 minutes
15. customThis removes the fumaric acid analog of compound 4
16. filtrationThe solid is then collected by filtration
17. washwashed successively with 0.1 N HCl and water
18. dry with materialfinally dried in a vacuum desiccator over P2O5

ORD record

ord-1213f801c1074514ae74551fcceafc21

Source dataset

uspto-grants-1986_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04618492