Trifluoroacetic acid → (2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)methanol

HRID 2066628Notes

Reaction equation

HRID 2066628 reaction equation
FC(F)(F)C(O)=O.C(OC1C=CC(C[O:21][CH2:22][C:23]2([CH3:34])[O:27][C:26]3=[N:28][C:29]([N+:31]([O-:33])=[O:32])=[CH:30][N:25]3[CH2:24]2)=CC=1)C1C=CC=CC=1.C1(OC)C=CC=CC=1>C(Cl)Cl>[CH3:34][C:23]1([CH2:22][OH:21])[O:27][C:26]2=[N:28][C:29]([N+:31]([O-:33])=[O:32])=[CH:30][N:25]2[CH2:24]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 509136332-({[4-(Benzyloxy)benzyl]oxy}methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole

Product 1

HCID 23081240(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (25.4 mL, 0.342 mol) was added dropwise to a stirred mixture of 2-({[4-(benzyloxy)benzyl]oxy}methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole (26) (see Example 2Z) (2.53 g, 6.40 mmol) and anisole (7.0 mL, 64 mmol) in CH2Cl2 (100 mL) (water bath cooling). After stirring at room temperature for 4 h, the solvents were removed by blowing under a stream of N2. The oily residue was treated with excess solid NaHCO3, then diluted with 15% MeOH/CH2Cl2 (100 mL), and the mixture was stirred at room temperature for 30 min and then filtered. The filtrate was evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% MeOH/CH2Cl2 firstly gave foreruns, and then further elution with 1-2% MeOH/CH2Cl2 gave (2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazol-2-yl)methanol (101) (reported by Tsubouchi et al., WO 2004033463A1 via 3 steps, starting from 2-chloro-4(5)-nitroimidazole (81) and 2-[methoxymethoxy)methyl]-2-methyloxirane) (1.215 g, 95%) as a cream solid: mp (MeOH/CH2Cl2/hexane) 174-176° C.; 1H NMR [(CD3)2SO] δ 8.09 (s, 1H), 5.41 (t, J=5.7 Hz, 1H), 4.24 (d, J=10.6 Hz, 1H), 4.03 (d, J=10.7 Hz, 1H), 3.64 (dd, J=12.2, 5.6 Hz, 1H), 3.54 (dd, J=12.2, 5.9 Hz, 1H), 1.51 (s, 3H). Anal. (C7H9N3O4) C, H, N.

Workup

  1. customthe solvents were removed
  2. additionThe oily residue was treated with excess solid NaHCO3
  3. additiondiluted with 15% MeOH/CH2Cl2 (100 mL)
  4. stirringthe mixture was stirred at room temperature for 30 min
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was chromatographed on silica gel
  8. washElution with 0-1% MeOH/CH2Cl2 firstly gave foreruns
  9. washfurther elution with 1-2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-1c6c51fb614f4c3396bb0c4ad7183f60
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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