1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

HRID 1259979Notes

Reaction equation

HRID 1259979 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:36]([OH:38])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCC[N:47]([CH3:49])C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:61][O:62]CN>CN(C=O)C.O.C(N(CC)CC)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][N:25]1[C:24]2[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=2[N:22]=[C:21]1[C:19]([N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C@H:12]1[CH2:11][C@@H:10]([C:36](=[O:38])[N:47]([O:62][CH3:61])[CH3:49])[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13]1)=[O:20]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21959107Methoxymethanamine hydrochlorideHCID 58355779(3R,5S)-(tert-butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid

Product 1

HCID 58355290tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (7.5 g), WSC.HCL (4.06 g) and HOBt (3.25 g) were dissolved in DMF (50 ml), N-methoxymethylamine hydrochloride (1.38 g) and triethylamine (7.88 ml) were added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4-9:1) was concentrated under reduced pressure to give the object product (4.76 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (1:4-9:1)
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-bd985ac55a734113b3301f4e9038e57f
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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