Triethylamine → 1075744-31-8

HRID 453714Notes

Reaction equation

HRID 453714 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[N:10]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C:18]3([OH:32])[CH2:23][CH:22]4[CH2:24][CH2:25][CH:19]3[CH:20]=[C:21]4[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:8][C:7]=2[C:6]([O:34][CH3:35])=[CH:5][CH:4]=1.CCN(CC)CC.[C:43](Cl)(=[O:47])[CH:44]([CH3:46])[CH3:45]>C(Cl)Cl>[CH3:35][O:34][C:6]1[C:7]2[N:8]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C@:18]3([O:32][C:43](=[O:47])[CH:44]([CH3:46])[CH3:45])[CH2:23][C@H:22]4[CH2:24][CH2:25][C@@H:19]3[CH:20]=[C:21]4[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:10][C:11]=2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 66877393HCID 66877393, compound

Product 1

HCID 442477241075744-31-8

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 199 mg of rac-(1R*,2R*,4R*)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol in 4 mL DCM were added 0.2 mL of NEt3 and 0.1 mL of isobutyrylchloride at 0° C. The reaction mixture was stirred overnight allowing the temperature to reach slowly rt. The reaction was quenched with sat. aq. NaHCO3, the phases were separated and the water phase was re-extracted with DCM. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was redissolved in 3 mL EtOAc, silica gel and 1.5 mL MeOH were added and the mixture was stirred vigorously for 7 d. The mixture was filtered, thouroughly washed with EtOAc-MeOH (2:1) and evaporated. Purification by CC using EtOAc-MeOH (5:1 to 3:1+0.1% NEt3) yielded 186 mg of rac-isobutyric acid (1R*,2R*,4R*)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester as beige foam.

Workup

  1. customto reach slowly rt
  2. customThe reaction was quenched with sat. aq. NaHCO3
  3. customthe phases were separated
  4. extractionthe water phase was re-extracted with DCM
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was redissolved in 3 mL EtOAc
  9. additionsilica gel and 1.5 mL MeOH were added
  10. stirringthe mixture was stirred vigorously for 7 d
  11. filtrationThe mixture was filtered
  12. washthouroughly washed with EtOAc-MeOH (2:1)
  13. customevaporated
  14. customPurification by CC

Sources & evidence

ORD record
ord-e2dc0f5f7e5347a487c6a99e26b93052
Source dataset
uspto-grants-2013_07
Patent number
US08492555B2

Reaction notes

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