Piperazine → 1-[5-(4-Fluoro-Phenyl)-4-(2,2,2-Trifluoro-Ethoxymethyl)-Oxazol-2-yl]-Piperazine

HRID 2288990Notes

Reaction equation

HRID 2288990 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11](S(C)(=O)=O)=[N:10][C:9]=2[CH2:17][O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:4][CH:3]=1.[NH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([N:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[N:10][C:9]=2[CH2:17][O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4837PiperazineHCID 187004355-(4-Fluoro-phenyl)-2-methanesulfonyl-4-(2,2,2-trifluoro-ethoxymethyl)-oxazole

Product 1

HCID 187004001-[5-(4-Fluoro-Phenyl)-4-(2,2,2-Trifluoro-Ethoxymethyl)-Oxazol-2-yl]-PiperazineYield 86%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-(4-Fluoro-phenyl)-2-methanesulfonyl-4-(2,2,2-trifluoro-ethoxymethyl)-oxazole (0.30 g; 0.85 mmol) in dry dioxane (6 ml) is treated with piperazine (0.37 g; 4.25 mmol) and heated in a pressure tube at 170 C. for 16 hours. The reaction mixture is partitioned between ethyl acetate (50 ml) and water (20 ml). The aqueous phase is washed with ethyl acetate (20 ml). The combined organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (5%-20%) afforded the product as a light yellow solid (0.26 g; 86%). HNMR (CDCl3): 7.55 (m, 2H), 7.14 (t, 2H, J=8.8 Hz), 4.65 (s, 2H), 4.03 (qt, 2H, J=9.0 Hz), 3.57 (t, 4H, J=4.9 Hz), 3.01 (t, 4H, J=4.9 Hz). Mass spectrum: m/e calculated (MH+)=360; observed (MH+)=360.

Workup

  1. temperatureheated in a pressure tube at 170 C
  2. customThe reaction mixture is partitioned between ethyl acetate (50 ml) and water (20 ml)
  3. washThe aqueous phase is washed with ethyl acetate (20 ml)
  4. washThe combined organic phases are washed with saturated brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (5%-20%)

Sources & evidence

ORD record
ord-6bebd684ead74890b77d65c07a489e5d
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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