Acetic Acid → HCID 69479141, compound

HRID 856276Notes

Reaction equation

HRID 856276 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=O)OC(C)(C)C)[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:35][C:36]([F:46])([F:45])[C:37]1[CH:44]=[CH:43][C:40](C=O)=[CH:39][CH:38]=1.[B-]C#N.[Na+].C(O)(=O)C>C(Cl)Cl>[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:15][CH2:16][CH:17]([NH:20][CH2:21][C:40]3[CH:43]=[CH:44][C:37]([C:36]([F:46])([F:45])[F:35])=[CH:38][CH:39]=3)[CH2:18][CH2:19]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 679964-(Trifluoromethyl)benzaldehydeHCID 20587905Sodium cyanoborohydride [MI]HCID 131726573HCID 131726573, compound

Product 1

HCID 69479141HCID 69479141, compoundYield 22.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (S)-[1-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperidin-4-yl]carbamate prepared in Example 283 (0.300 g, 0.787 mmol) was dissolved in methylene chloride (4 ml). To the solution, trifluoroacetic acid (2 ml) was added followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and added methylene chloride (4 ml) and triethylamine (4 ml). The mixture was stirred at room temperature for 20 minutes and then concentrated under reduced pressure. The residue was dissolved in methanol (5 ml). To the solution, 4-trifluoromethylbenzaldehyde (0.164 g, 0.945 mmol), sodium cyanotrihydroborate (0.099 g, 1.57 mmol) and acetic acid (0.09 ml, 1.57 mmol) were added followed by stirring at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure. To the residue, water was added, and the solution was extracted with methylene chloride. The organic phases were combined, washed with a saturated saline solution, dried over sodium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1) and recrystallized from isopropyl alcohol to afford (S)-N-[1-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperidin-4-yl]-4-trifluoromethylbenzylamine (0.078 g, yield 22%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (4 ml) and triethylamine (4 ml)
  3. stirringThe mixture was stirred at room temperature for 20 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in methanol (5 ml)
  6. stirringby stirring at room temperature for 4 hours
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. additionTo the residue, water was added
  9. extractionthe solution was extracted with methylene chloride
  10. washwashed with a saturated saline solution
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationThe resulting filtrate was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1)
  15. customrecrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-6f28ea04bf8c472d870e71e6d7e5614e
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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