2,2,6,6-Tetramethylpiperidine → (2'R,6'S)-1'-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2';6',2'']terpyridine

HRID 1987325Notes

Reaction equation

HRID 1987325 reaction equation
[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:21]([N:28]1[CH2:32][C:31]([CH2:33][CH2:34]OS(C)(=O)=O)=[CH:30][NH:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC1(C)CCCC(C)(C)N1>CC#N>[CH2:21]([N:28]1[CH2:32][C:31]([CH2:33][CH2:34][N:9]2[C@H:8]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[CH2:13][CH2:12][CH2:11][C@@H:10]2[C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:30][NH:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 130352,2,6,6-TetramethylpiperidineHCID 575911373,3''-Dimethyl-1',2',3',4',5', 6'-hexahydro-cis-[2,2';6',2'']terpyridineHCID 86597121methanesulfonic acid 2-(2-benzyl-1H-pyrazol-4-yl)-ethyl ester

Product 1

HCID 86597120(2'R,6'S)-1'-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2';6',2'']terpyridineYield 93%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (2′R,6′S)-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′2″]terpyridine (0.320 g, 1.20 mmol), methanesulfonic acid 2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl ester (0.540 g, 1.60 mmol) and 2,2,6,6-tetramethylpiperidine (0.255 g, 1.80 mmol) in CH3CN (5 mL) was stirred and heated at reflux overnight. The solvent was then removed, water (20 mL) was added, and the mixture was extracted with CH2Cl2 (3×20 mL). The extracts were combined and dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (500:15:1 CH2Cl2/CH3OH/NH4OH), affording (2′R,6′S)-1′-[2-(2-benzyl-1H-pyrazol-4-yl)-ethyl]-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine as a pale yellow oil (0.420 g, 93%).

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. customThe solvent was then removed
  4. additionwater (20 mL) was added
  5. extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed by evaporation under vacuum
  9. customthe residue was purified by flash chromatography on a silica gel column (500:15:1 CH2Cl2/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-494041b838574bb1bb31449b83da0613
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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