Trifluoroacetic acid → (S)-2-methyl-6-nitro-2-[4-{1-[3-(4-trifluoromethoxyphenyl)-2-propenyl]piperidin-4-yl}piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856382Notes

Reaction equation

HRID 856382 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](OC(C)(C)C)=O)[CH2:22][CH2:21]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.FC(F)(F)C(O)=O.[F:40][C:41]([F:54])([F:53])[O:42][C:43]1[CH:48]=[CH:47][C:46]([CH:49]=[CH:50]C=O)=[CH:45][CH:44]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH:50]=[CH:49][C:46]4[CH:45]=[CH:44][C:43]([O:42][C:41]([F:40])([F:53])[F:54])=[CH:48][CH:47]=4)[CH2:22][CH2:21]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

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 533949673-(4-Trifluoromethoxyphenyl)propenalHCID 69635208tert-butyl (S)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]piperidine-1-carboxylate

Product 1

HCID 69480259(S)-2-methyl-6-nitro-2-[4-{1-[3-(4-trifluoromethoxyphenyl)-2-propenyl]piperidin-4-yl}piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazoleYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (S)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]piperidine-1-carboxylate (750 mg, 1.66 mmol) was dissolved in methylene chloride (5 ml), trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 1.5 hours. The reaction mixture was concentrated. To the residue, methylene chloride (5 ml) and triethylamine (5 ml) were added, and the mixture was stirred at room temperature for 10 minutes and then concentrated. The residue was dissolved in 1,2-dichloroethane (20 ml), 3-(4-trifluoromethoxyphenyl)propenal (396 mg, 1.83 mmol) and sodium triacetoxyborohydride (564 mg, 2.66 mmol) were added followed by stirring at room temperature for 3.5 hours. The reaction solution was washed with a saturated sodium hydrogencarbonate solution (15 ml), water (20 ml), and a saturated saline solution (20 ml) in this order, and then dried over sodium sulfate. After filtration, the filtrate was concentrated, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1) and then recrystallized from methanol/water to obtain (S)-2-methyl-6-nitro-2-[4-{1-[3-(4-trifluoromethoxyphenyl)-2-propenyl]piperidin-4-yl}piperazin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole (446 mg, 49%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionTo the residue, methylene chloride (5 ml) and triethylamine (5 ml) were added
  3. stirringthe mixture was stirred at room temperature for 10 minutes
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 1,2-dichloroethane (20 ml)
  6. stirringby stirring at room temperature for 3.5 hours
  7. washThe reaction solution was washed with a saturated sodium hydrogencarbonate solution (15 ml), water (20 ml)
  8. dry with materiala saturated saline solution (20 ml) in this order, and then dried over sodium sulfate
  9. filtrationAfter filtration
  10. concentrationthe filtrate was concentrated
  11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1)
  12. customrecrystallized from methanol/water

Sources & evidence

ORD record
ord-78db9b48d9624312bd071f86b36aacf5
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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