Sodium Carbonate → Tert-butyl 4-{2-[1-(6-methylpyridin-2-yl)piperidin-4-yl]ethyl}piperidine-1-carboxylate

HRID 2074340Notes

Reaction equation

HRID 2074340 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.Cl.[NH:27]1[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)[CH2:29][CH2:28]1.Cl[C:49]1[CH:54]=[CH:53][CH:52]=[C:51]([CH3:55])[N:50]=1.CC(C)([O-])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd].C1(C)C=CC=CC=1>[CH3:55][C:51]1[N:50]=[C:49]([N:27]2[CH2:28][CH2:29][CH:30]([CH2:33][CH2:34][CH:35]3[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40]3)[CH2:31][CH2:32]2)[CH:54]=[CH:53][CH:52]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 876016-Chloro-2-picolineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 57421848Tert-butyl 4-[2-(piperidin-4-yl)ethyl]piperidine-1-carboxylate hydrochloride

Product 1

HCID 57507817Tert-butyl 4-{2-[1-(6-methylpyridin-2-yl)piperidin-4-yl]ethyl}piperidine-1-carboxylateYield 50.4%

Reagents, catalysts & solvents 2

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

2-(Dicyclohexylphosphino)biphenyl (71 mg) and (1E,4E)-1,5-diphenyl-1,4-pentadien-3-one-palladium (93 mg) were added to a toluene (10 ml) suspension of tert-butyl 4-(2-piperidin-4-ylethyl)piperidine-1-carboxylate hydrochloride (1.13 g), 2-chloro-6-methylpyridine (431 mg) and sodium tert-butoxide (487 mg), followed by stirring at 120° C. for 1 hour. The reaction liquid was left cooled, then an aqueous saturated sodium carbonate solution was added thereto, followed by extraction with EtOAc. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated and the residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=10:1 (v/v)) to obtain tert-butyl 4-{2-[1-(6-methylpyridin-2-yl)piperidin-4-yl]ethyl}piperidine-1-carboxylate (660 mg) as a red oil.

Workup

  1. customThe reaction liquid
  2. waitwas left
  3. temperaturecooled
  4. extractionfollowed by extraction with EtOAc
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThen, the solvent was evaporated
  8. customthe residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=10:1 (v/v))

Sources & evidence

ORD record
ord-48ffc657188f424b84d45be16d14c2ef
Source dataset
uspto-grants-2011_04
Patent number
US07919495B2

Reaction notes

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