1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 57855835, compound

HRID 475572Notes

Reaction equation

HRID 475572 reaction equation
[F:1][CH:2]([F:27])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][NH:16][C:17](=[O:25])[C:18]3[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][N:19]=3)[N:14]=2)=[CH:6][C:5]=1[OH:26].N12CCCN=[C:34]1[CH2:33][CH2:32][CH2:31]CC2.BrCC1CC1>C(O)C>[CH:33]1([CH2:34][O:26][C:5]2[CH:6]=[C:7]([C:10]3[O:11][CH:12]=[C:13]([CH2:15][NH:16][C:17](=[O:25])[C:18]4[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][N:19]=4)[N:14]=3)[CH:8]=[CH:9][C:4]=2[O:3][CH:2]([F:1])[F:27])[CH2:31][CH2:32]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81503BromomethylcyclopropaneHCID 68984051HCID 68984051, compound

Product 1

HCID 57855835HCID 57855835, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

0.12 g of N-[2-(4-difluoromethoxy-3-hydroxyphenyl)oxazol-4-ylmethyl]-3-methylpicolinamide obtained in Example 97 and 0.15 ml of 1,8-diazabicyclo[5,4,0]undec-7-ene were dissolved in 4 ml of ethanol. 0.15 ml of (bromomethyl)cyclopropane was added thereto and refluxed with heating for 3 hours. The solvent was distilled off, and water was added to the residue. Ethyl acetate extraction was performed. The organic layer was washed twice with water, and concentrated. The residue was purified by silica gel column choromatography (n-hexane:ethyl acetate=1:1). The obtained crude crystals were recrystallized using an ethanol-n-hexane mixture, and 60 mg of white powdery N-[2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)oxazol-4-ylmethyl]-3-methylpicolinamide was obtained.

Workup

  1. temperaturerefluxed
  2. temperaturewith heating for 3 hours
  3. distillationThe solvent was distilled off
  4. additionwater was added to the residue
  5. extractionEthyl acetate extraction
  6. washThe organic layer was washed twice with water
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column choromatography (n-hexane:ethyl acetate=1:1)
  9. customThe obtained crude crystals
  10. customwere recrystallized

Sources & evidence

ORD record
ord-100427bb584147cd8ae6dd8f6b27bff7
Source dataset
uspto-grants-2014_01
Patent number
US08637559B2

Reaction notes

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