Formic Acid → HCID 25191984, compound

To a solution of tropane (2.5 g, 20 mmol) in toluene (80 ml) was slowly added [2,2,2]-trichloroethyl chloroformate (20 ml, 94.4 mmol) and Na2CO3(1.5 g, 14 mmol). The mixture was heated to 110° C. overnight. The solution was cooled to room temperature, ethyl acetate (150 ml), water (100 ml) and H2SO4 (→pH 2) were added. The organic phase was dried over sodium sulfate, and concentrated under vacuum to yield 9.3 g colorless oil. The preceding product (3.3 g) was dissolved in THF (50 ml) and methanol (50 ml), and freshly prepared Zn/Cu (15 g) was added followed by formic acid (5 ml). The mixture was stirred at room temperature for 20 minutes before filtering the solids and evaporating the solvent until ˜10 ml remained. Concentrated sodium hydroxide solution was added until pH 10 was reached and the mixture extracted with chloroform (100 ml) and the organic phase dried over sodium sulfate. Triethylamine (2 ml) was added followed by a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (0.5 g, 2.73 mmol) in chloroform (20 ml), slowly. After stirring the mixture for 20 minutes, water (100 ml) and H2SO4 (→pH2) were added and the aqueous phase extracted with chloroform (100 ml), dried over magnesium sulfate, and concentrated under vacuum to give an oil. The material was purified by silica gel chromatography eluting with hexane/ethyl acetate (3:2), to give after crystallization from dicloromethane/MTBE 133 mg of a white solid: mp=128-130° C., LC-MS, MH+=258; 1H NMR (300 MHz, CDCl3) δ 7.92 (s, 1H); 7.90 (d, 1H, J=6.3 Hz); 7.52 (d, 1H, J=6.3 Hz); 4.84 (s, 1H); 4.06 (s, 1H); 2.06-1.50 ppm (m, 10H).

1. filtrationbefore filtering the solids
2. customevaporating the solvent until ˜10 ml
3. additionConcentrated sodium hydroxide solution was added until pH 10
4. extractionthe mixture extracted with chloroform (100 ml)
5. dry with materialthe organic phase dried over sodium sulfate
6. additionTriethylamine (2 ml) was added
7. stirringAfter stirring the mixture for 20 minutes
8. extractionthe aqueous phase extracted with chloroform (100 ml)
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated under vacuum
11. customto give an oil
12. customThe material was purified by silica gel chromatography
13. washeluting with hexane/ethyl acetate (3:2)
14. customto give
15. customafter crystallization from dicloromethane/MTBE 133 mg of a white solid

ORD record

ord-fe525cb5633c420996d1ab0ab68b24cb

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263591B2