Acetic Acid → (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856226Notes

Reaction equation

HRID 856226 reaction equation
[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([C:27](OC(C)(C)C)=O)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[F:48][C:49]([F:59])([F:58])[C:50]1[CH:57]=[CH:56][C:53](C=O)=[CH:52][CH:51]=1.[B-]C#N.[Na+].C(O)(=O)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([CH2:27][C:53]4[CH:56]=[CH:57][C:50]([C:49]([F:59])([F:58])[F:48])=[CH:51][CH:52]=4)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1

Participants

9

Reactant 7

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 679964-(Trifluoromethyl)benzaldehydeHCID 516892Sodium BicarbonateHCID 20587905Sodium cyanoborohydride [MI]HCID 67274388tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

Product 1

HCID 10006788(R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)-phenyl]piperazine-1-carboxylate prepared in Example 148 (800 mg, 1.74 mmol) and trifluoroacetic acid (3 ml) was stirred at room temperature for 7 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride (10 ml). To the solution, triethylamine (3 ml, 21.52 mmol) was added followed by stirring at room temperature for 5 minutes. The mixture was concentrated under reduced pressure, and the residue was dissolved in methanol (10 ml). To the solution, 4-trifluoromethylbenzaldehyde (910 mg, 5.23 mmol), sodium cyanotrihydroborate (328 mg, 5.23 mmol) and acetic acid (0.33 ml, 5.23 mmol) were added followed by stirring at room temperature overnight. To the reaction mixture, a saturated sodium hydrogencarbonate solution and methylene chloride were added, and the solution was stirred and then extracted with methylene chloride. The organic phase was dried over magnesium sulfate and filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (667 mg, yield 74%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in methylene chloride (10 ml)
  3. stirringby stirring at room temperature for 5 minutes
  4. concentrationThe mixture was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (10 ml)
  6. stirringby stirring at room temperature overnight
  7. stirringthe solution was stirred
  8. extractionextracted with methylene chloride
  9. dry with materialThe organic phase was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe resulting filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)

Sources & evidence

ORD record
ord-0e1922be55e14a54afba3ea635aff7a6
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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