Acetic Acid → (S)-2-methyl-6-nitro-2-[4-(4'-trifluoromethylbiphenyl-4-ylmethyl)piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856314Notes

Reaction equation

HRID 856314 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20](OC(C)(C)C)=O)[CH2:16][CH2:15]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.[F:34][C:35]([F:51])([F:50])[C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:47]=[CH:46][C:45](C=O)=[CH:44][CH:43]=2)=[CH:38][CH:37]=1.[B-]C#N.[Na+].C(O)(=O)C>C(Cl)Cl>[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:45]3[CH:44]=[CH:43][C:42]([C:39]4[CH:40]=[CH:41][C:36]([C:35]([F:34])([F:50])[F:51])=[CH:37][CH:38]=4)=[CH:47][CH:46]=3)[CH2:16][CH2:15]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

7

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 27827124'-(Trifluoromethyl)-4-biphenylcarbaldehydeHCID 20587905Sodium cyanoborohydride [MI]HCID 69635111tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

Product 1

HCID 10097539(S)-2-methyl-6-nitro-2-[4-(4'-trifluoromethylbiphenyl-4-ylmethyl)piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazoleYield 63.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylate prepared in Example 393 (1.7 g, 4.6 mmol), trifluoroacetic acid (10 ml) and methylene chloride (30 ml) was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methanol (30 ml). To the solution, 4′-trifluoromethylbiphenyl-4-carboaldehyde (2.3 g, 9.19 mmol), sodium cyanotrihydroborate (580 mg, 9.23 mmol) and acetic acid (0.55 ml, 9.62 mmol) were added in this order followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure. To the residue, a saturated sodium hydrogencarbonate solution was added, and the solution was extracted with methylene chloride twice. The organic phases were combined, washed with a saturated sodium hydrogencarbonate solution and a saturated saline solution in this order, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) to afford (S)-2-methyl-6-nitro-2-[4-(4′-trifluoromethylbiphenyl-4-ylmethyl)piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole (1.47 g, yield 63%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methanol (30 ml)
  3. stirringby stirring at room temperature overnight
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionTo the residue, a saturated sodium hydrogencarbonate solution was added
  6. extractionthe solution was extracted with methylene chloride twice
  7. washwashed with a saturated sodium hydrogencarbonate solution
  8. dry with materiala saturated saline solution in this order, dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1)

Sources & evidence

ORD record
ord-89fa4cf8564e49548f3f40eb1fb68885
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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