Acetic Acid → HCID 69483055, compound

HRID 856313Notes

Reaction equation

HRID 856313 reaction equation
[N+:1]([C:4]1[N:5]=[C:6]2[N:10]([CH:11]=1)[CH2:9][C@@H:8]([CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19](OC(C)(C)C)=O)[CH2:15][CH2:14]1)[O:7]2)([O-:3])=[O:2].FC(F)(F)C(O)=O.C(N(CC)CC)C.[C:40]1([C:46]2[CH:53]=[CH:52][C:49](C=O)=[CH:48][CH:47]=2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[B-]C#N.[Na+].C(O)(=O)C>>[C:40]1([C:46]2[CH:47]=[CH:48][CH:49]=[CH:52][CH:53]=2)[CH:45]=[CH:44][C:43]([CH2:19][N:16]2[CH2:15][CH2:14][N:13]([CH2:12][C@H:8]3[O:7][C:6]4=[N:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:11][N:10]4[CH2:9]3)[CH2:18][CH2:17]2)=[CH:42][CH:41]=1

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 76689(1,1'-Biphenyl)-4-carboxaldehydeHCID 20587905Sodium cyanoborohydride [MI]HCID 69635394HCID 69635394, compound

Product 1

HCID 69483055HCID 69483055, compoundYield 46%

Procedure

A mixture of tert-butyl (R)-4-(6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 395 (101.5 mg, 0.29 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 (2 ml, 14.35 mmol), and then the solution was concentrated under reduced pressure. The residue was dissolved in methanol (5 ml). To the solution, 4-phenylbenzaldehyde (156 mg, 0.86 mmol), sodium cyanotrihydroborate (53 mg, 0.84 mmol) and acetic acid (0.05 ml, 0.87 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 (ethyl acetate) to afford (R)-2-[4-(biphenyl-4-ylmethyl)piperazin-1-ylmethyl]-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (56 mg, yield 46%) as a white powder.

Workup

  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 overnight
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. additionTo the residue, a saturated sodium hydrogencarbonate solution was added
  8. extractionthe solution was extracted with methylene chloride twice
  9. washwashed with a saturated sodium hydrogencarbonate solution
  10. dry with materiala saturated saline solution in this order, dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-8d43d9f9172d42239dcaf8a14511a58a
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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