Trifluoroacetic anhydride → tert-butyl (3S,5R)-3-[{[1-(2-cyanoethyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1184181Notes

Reaction equation

HRID 1184181 reaction equation
[NH2:1][C:2](=O)[CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]([N:16]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:24])[CH2:20][N:19]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:18]1)=[O:15].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:2]([CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]([N:16]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)=[O:24])[CH2:20][N:19]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:18]1)=[O:15])#[N:1]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 58355743HCID 58355743, compound

Product 1

HCID 58355281tert-butyl (3S,5R)-3-[{[1-(2-cyanoethyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 87.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

tert-Butyl(3S, 5R)-3-[{[1-(3-amino-3-oxopropyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (233 mg) was dissolved in pyridine (5 ml), trifluoroacetic anhydride (116 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 aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (7:3) was concentrated under reduced pressure to give the object product (197 mg).

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 aqueous sodium bicarbonate and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washa fraction eluted with ethyl acetate-hexane (7:3)
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-39180177dc9f48f4831b85f77c09f6b5
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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