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 1184113Notes

Reaction equation

HRID 1184113 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-f19c8dcbee7b46a0b0694433383dda92
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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