Acetic Acid → 2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole

A mixture of tert-butyl (R)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylate prepared in Example 396 (100 mg, 0.27 mmol) and trifluoroacetic acid (2 ml) was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride (5 ml) and neutralized with triethylamine (1 ml, 7.17 mmol), and then the solution was concentrated under reduced pressure. The residue was dissolved in methanol (5 ml). To the solution, 4-phenylbenzaldehyde (149 mg, 0.82 mmol), sodium cyanotrihydroborate (51 mg, 0.82 mmol) and acetic acid (48 μl, 0.82 mmol) were added in this order followed by stirring at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was added a saturated sodium hydrogencarbonate solution. The precipitates were filtered off and purified by silica gel column chromatography (ethyl acetate) to afford (R)-2-(biphenyl-4-ylmethyl)piperazin-1-ylmethyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (67 mg, yield 57%) as a light yellow powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionThe residue was dissolved in methylene chloride (5 ml)
3. concentrationthe solution was concentrated under reduced pressure
4. dissolutionThe residue was dissolved in methanol (5 ml)
5. stirringby stirring at room temperature for 15 hours
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. additionthe residue was added a saturated sodium hydrogencarbonate solution
8. filtrationThe precipitates were filtered off
9. custompurified by silica gel column chromatography (ethyl acetate)

ORD record

ord-3b192b10286e43d1a0710dea2e6d600e

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2