Potassium Carbonate → Tert-butyl 4-(pyridin-4-ylmethyl)piperidine-1-carboxylate

HRID 1869619Notes

Reaction equation

HRID 1869619 reaction equation
C12BC(CCC1)CCC2.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20](=[CH2:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].Br[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.ClCCl.CN(C)C=O>[N:28]1[CH:29]=[CH:30][C:25]([CH2:23][CH:20]2[CH2:21][CH2:22][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:18][CH2:19]2)=[CH:26][CH:27]=1

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 142684-BromopyridineHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-Methylenepiperidine

Product 1

HCID 18539261Tert-butyl 4-(pyridin-4-ylmethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

9-borabicyclo[3.3.1]nonane (101.5 ml of a 0.5M solution in tetrahydrofuran) was added to a degassed sample of N-(tert-butoxycarbonyl)-4-methylene piperidine (may be prepared as described in A. Palani et al., J. Med. Chem., 2002, 45: 3145) (10 g) and the resultant solution heated at reflux for 1 h. After cooling to room temperature the reaction mixture was then added to a mixture of 4-bromopyridine (7.23 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g), K2CO3 (8.42 g), N,N-dimethylformamide (100 ml) and water (10 ml), and the resultant mixture heated at 60° C. for 3 h. After cooling to room temperature, another charge of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g) was added to the reaction and heated at 60° C. overnight. The mixture was cooled to room temperature and poured into water, the pH was adjusted to 11 by the addition of 10% aqueous sodium hydroxide and extracted into ethyl acetate. Combined organic extracts were dried (Na2SO4) and evaporated to give the crude pyridine as a brown viscous oil. Chromatography [silica gel, eluting with ethyl acetate in hexanes, 0-100%] gave the title compound (D1) as a pale yellow oil (7.5 g).

Workup

  1. custommay be prepared
  2. temperatureat reflux for 1 h
  3. temperatureAfter cooling to room temperature
  4. additionwas added to the reaction
  5. temperatureheated at 60° C. overnight
  6. temperatureThe mixture was cooled to room temperature
  7. extractionextracted into ethyl acetate
  8. dry with materialCombined organic extracts were dried (Na2SO4)
  9. customevaporated
  10. customto give the crude pyridine as a brown viscous oil
  11. washChromatography [silica gel, eluting with ethyl acetate in hexanes, 0-100%]

Sources & evidence

ORD record
ord-5c7beca22c1b484781ea380afded6ff4
Source dataset
uspto-grants-2009_12
Patent number
US07638631B2

Reaction notes

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