Triacetoxyperiodinane → tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(pyrazine-2-carbonyl)-1H-benzo[d]imidazole-1-carboxylate

HRID 1773690Notes

Reaction equation

HRID 1773690 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([CH:26]([OH:33])[C:27]3[CH:32]=[N:31][CH:30]=[CH:29][N:28]=3)[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:11]=3[CH:25]=2)=[C:5]([CH3:34])[O:4][N:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:26]([C:27]3[CH:32]=[N:31][CH:30]=[CH:29][N:28]=3)=[O:33])[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[N:12]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[C:11]=3[CH:25]=2)=[C:5]([CH3:34])[O:4][N:3]=1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 117601903tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(hydroxy(pyrazin-2-yl)methyl)-1H-benzo[d]imidazole-1-carboxylate

Product 1

HCID 117601616tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(pyrazine-2-carbonyl)-1H-benzo[d]imidazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2,2,6,6-tetramethylpiperidine (0.27 mL, 1.56 mmol) in tetrahydrofuran (16 mL) at −78° C. was added n-butyllithium (0.97 mL, 1.56 mmol, 1.6 M in hexanes). After 5 minutes, the reaction was warmed to 0° C. After stirring for 30 minutes, the reaction was cooled to −78° C., and pyrazine (137 mg, 1.69 mmol) in tetrahydrofuran (3.3 mL) and tert-butyl dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-indole-1-carboxylate (498 mg, 1.3 mmol) in tetrahydrofuran (2.6 mL) were added simultaneously in a drop-wise manner. After stirring for 60 minutes, the reaction was quenched with saturated NH4Cl(aq) (10 mL), extracted with ethyl acetate (3×10 mL), dried over Na2SO4, and concentrated in vacuo. Purification by flash chromatography (0-100% ethyl acetate/hexane) afforded tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(hydroxy(pyrazin-2-yl)methyl)-1H-benzo[d]imidazole-1-carboxylate. To tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(hydroxy(pyrazin-2-yl)methyl)-1H-benzo[d]imidazole-1-carboxylate (50 mg, 0.11 mmol) in dichloromethane (2.5 mL) was added Dess-Martin periodinane (72.4 mg, 0.16 mmol). After 15 minutes, the reaction was quenched with saturated Na2S2O3(aq) (10 mL) and extracted with dichloromethane (3×10 mL), dried over Na2SO4, and concentrated in vacuo. Purification by flash chromatography (0-100% ethyl acetate/hexanes) afforded tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(pyrazine-2-carbonyl)-1H-benzo[d]imidazole-1-carboxylate as a yellow oil.

Workup

  1. customthe reaction was quenched with saturated Na2S2O3(aq) (10 mL)
  2. extractionextracted with dichloromethane (3×10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-01d19b1df80d476ebe0fdbf8944fe151
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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