Trifluoroacetic acid → (S)-2-chloro-1-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]ethanone

HRID 856316Notes

Reaction equation

HRID 856316 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:21])[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.C(N(CC)CC)C.[Cl:41][CH2:42]C(Cl)=O>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:41][CH2:42][C:20]([N:17]1[CH2:16][CH2:15][N:14]([CH2:13][C@:2]2([CH3:1])[O:6][C:5]3=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]3[CH2:3]2)[CH2:19][CH2:18]1)=[O:21]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 69635111tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

Product 1

HCID 69481407(S)-2-chloro-1-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]ethanoneYield 43%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 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 (1.5 g, 4.1 mmol) and trifluoroacetic acid (20 ml) was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride (20 ml), and the solution was added triethylamine (3 ml) and 4-dimethylaminopyridine (100 mg, 0.82 mmol) in this order. To the mixture, a solution of chloroacetyl chloride (0.49 ml, 6.2 mmol) in methylene chloride (2 ml) was added slowly with cooling on ice-bath followed by stirring at room temperature overnight. The reaction mixture was washed with water twice, 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=100/1) to afford (S)-2-chloro-1-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]ethanone (600 mg, yield 43%) as a light brown powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methylene chloride (20 ml)
  3. temperaturewith cooling on ice-bath
  4. stirringby stirring at room temperature overnight
  5. washThe reaction mixture was washed with water twice
  6. dry with materiala saturated sodium hydrogencarbonate solution and a saturated saline solution in this order, dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)

Sources & evidence

ORD record
ord-aa01a6dbc3c44a398d31082fb75960f0
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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