Acetic Acid → (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride

A stirred mixture of (R)-6,8-difluorochroman-3-ylamine hydrochloride (1.68 g, 7.58 mmol), [4-(tert-butyldimethylsilanyloxy)-3-oxobutyl]carbamic acid tert-butyl ester (3.13 g, 9.85 mmol), potassium thiocyanate (0.96 g, 9.85 mmol), water (0.18 mL, 10 mmol) and acetic acid (3.0 mL, 50 mmol) in ethyl acetate (30 mL) was refluxed for 7 hours, cooled to room temperature, washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate—petroleum ether mixture as eluent. The resulting oil (2.15 g) was dissolved in ethyl acetate (20 ml), 2M HCl solution in ethyl acetate was added (20 mL, 40 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals, which decomposed without melting.

1. temperaturewas refluxed for 7 hours
2. washwashed by sodium bicarbonate solution
3. dry with materialdried over anhydrous magnesium sulphate
4. customevaporated in vacuo
5. customThe residue was purified by column chromatography on silica
6. dissolutionThe resulting oil (2.15 g) was dissolved in ethyl acetate (20 ml)
7. addition2M HCl solution in ethyl acetate was added (20 mL, 40 mmol)
8. customThe precipitate was removed by filtration
9. washwashed with ethyl acetate
10. customto give crystals, which

ORD-Eintrag

ord-df33cdcc8d434ef1ad1a31d36688c222

Quelldatensatz

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07259271B2