Tetrahydrofuran → HCID 136149966, compound

HRID 2263415Notes

Reaction equation

HRID 2263415 reaction equation
[CH3:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[S:16][C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[N:14][C:13]=2[CH2:27][O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH2:36][OH:37].C(N(CC)CC)C.[O:45]1CCC[CH2:46]1>CO>[CH3:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[S:16][C:15]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=3)=[N:14][C:13]=2[CH2:27][O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:7]=[CH:6][C:3]=1[C:4]1[NH:5][C:46](=[O:45])[O:37][N:36]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 59594697HCID 59594697, compound

Product 1

HCID 136149966HCID 136149966, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

1.5 g 2-Methyl-4-[4-(tetrahydro-pyran-2-yloxymethyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-benzonitrile were dissolved in a mixture of 10 ml tetrahydrofuran and 10 ml methanol. 2.12 g hydroxylamine hydrochloride were added followed by the addition of 5.08 ml triethylamine. The reaction mixture was stirred at 65° C. overnight. The solvents were removed in vacuo and the resulting residue poured into water and extracted five times with ethylacetate. The combined organic extracts were washed with brine, dried over MgSO4 and the solvent was evaporated in vacuo. The residue was dissolved in 10 ml dichloromethane. 0.32 ml pyridine and 0.49 ml phenylchloroformate were added and the mixture stirred at room temperature for fifteen minutes. The mixture was diluted by the addition of 50 ml acetonitrile and 2.28 ml 1,8-diazabicyclo[5.4.0]undec-7-ene were added. The mixture was stirred at room temperature for thirty minutes. The mixture was evaporated in vacuo and the resulting crude material was purified by silica gel chromatography with the eluent n-heptane: ethyl acetate=4:1=>ethyl acetate=>ethyl acetate:methanol=4:1 to obtain 1.05 g 3-{2-methyl-4-[4-(tetrahydro-pyran-2-yloxymethyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one as pale yellow solid.

Workup

  1. customThe solvents were removed in vacuo
  2. additionthe resulting residue poured into water
  3. extractionextracted five times with ethylacetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. customthe solvent was evaporated in vacuo
  7. dissolutionThe residue was dissolved in 10 ml dichloromethane
  8. addition0.32 ml pyridine and 0.49 ml phenylchloroformate were added
  9. stirringthe mixture stirred at room temperature for fifteen minutes
  10. additionThe mixture was diluted by the addition of 50 ml acetonitrile and 2.28 ml 1,8-diazabicyclo[5.4.0]undec-7-ene
  11. additionwere added
  12. stirringThe mixture was stirred at room temperature for thirty minutes
  13. customThe mixture was evaporated in vacuo
  14. customthe resulting crude material was purified by silica gel chromatography with the eluent n-heptane

Sources & evidence

ORD record
ord-78cbf82e26d44692941bd6f601bc9478
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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