2-Bromopyridine → tert-butyl (3R,5S)-3-[hydroxy(pyridin-2-yl)methyl]-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl)carbonyl)(2-methylpropyl)amino)piperidine-1-carboxylate

HRID 1509440Notes

Reaction equation

HRID 1509440 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.CCCCCC.C([Li])CCC.[CH:19]([C@@H:21]1[CH2:26][C@H:25]([N:27]([C:32]([C:34]2[N:38]([CH2:39][CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:37]3[CH:45]=[CH:46][CH:47]=[CH:48][C:36]=3[N:35]=2)=[O:33])[CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:24][N:23]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:22]1)=[O:20].[Cl-].[NH4+]>C1COCC1>[OH:20][CH:19]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[C@@H:21]1[CH2:26][C@H:25]([N:27]([C:32]([C:34]2[N:38]([CH2:39][CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:37]3[CH:45]=[CH:46][CH:47]=[CH:48][C:36]=3[N:35]=2)=[O:33])[CH2:28][CH:29]([CH3:30])[CH3:31])[CH2:24][N:23]([C:49]([O:51][C:52]([CH3:53])([CH3:55])[CH3:54])=[O:50])[CH2:22]1

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 25517Ammonium ChlorideHCID 58355644tert-butyl (3R,5S)-3-formyl-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylateHCID 178418244HCID 178418244, compound

Product 1

HCID 58355751tert-butyl (3R,5S)-3-[hydroxy(pyridin-2-yl)methyl]-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl)carbonyl)(2-methylpropyl)amino)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of bromopyridine (0.058 ml) cooled to −78° C. in THF (5 ml) was added 1.6M-butyllithium hexane solution (0.33 ml) and the mixture was stirred for 30 min. A solution of tert-butyl (3R,5S)-3-formyl-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylate (257 mg) in THF (5 ml) was added and the mixture was stirred at −20° C. for 2 hr. The reaction mixture was poured into saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated 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 (1:1-1:0) was concentrated under reduced pressure to give the object product (100 mg).

Workup

  1. stirringthe mixture was stirred at −20° C. for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (1:1-1:0)
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-26416b512d58408d8c95bd2bee2a84f7
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

Loading…