Trifluoroacetic anhydride → tert-butyl (3R,5S)-3-cyano-5-{{{1-(4-methoxybutyl)-1H-benzimidazol-2-yl}carbonyl}(2-methylpropyl)amino}piperidine-1-carboxylate

HRID 1184147Notes

Reaction equation

HRID 1184147 reaction equation
[C:1]([C@@H:4]1[CH2:9][C@H:8]([N:10]([C:15]([C:17]2[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])[CH2:7][N:6]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:5]1)(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:1]([C@@H:4]1[CH2:9][C@H:8]([N:10]([C:15]([C:17]2[N:21]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)=[O:16])[CH2:11][CH:12]([CH3:13])[CH3:14])[CH2:7][N:6]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:5]1)#[N:2]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 58355659tert-Butyl (3R,5S)-3-carbamoyl-5-{{{1-(4-methoxybutyl)-1H-benzimidazol-2-yl}carbonyl}(2-methylpropyl)amino}piperidine-1-carboxylate

Product 1

HCID 58355698tert-butyl (3R,5S)-3-cyano-5-{{{1-(4-methoxybutyl)-1H-benzimidazol-2-yl}carbonyl}(2-methylpropyl)amino}piperidine-1-carboxylateYield 103.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

tert-Butyl (3R,5S)-3-carbamoyl-5-{{{1-(4-methoxybutyl)-1H-benzimidazol-2-yl}carbonyl}(2-methylpropyl)amino}piperidine-1-carboxylate (1.01 g) was dissolved in pyridine (10 ml), trifluoroacetic anhydride (570 μl) was added at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and diluted with ethyl acetate. 1M Hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected m to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate was concentrated under reduced pressure to give the object product (1.01 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with ethyl acetate
  3. addition1M Hydrochloric acid was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washa fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-d2a6402ff64a467e8c5f93f937a1d224
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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