2-Bromopyridine → N-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]methyl}pyridin-2-amine

HRID 273036Notes

Reaction equation

HRID 273036 reaction equation
[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([CH2:21][NH2:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([CH2:21][NH:22][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 23676156Sodium t-butoxideHCID 685780131-[4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]methanamine

Product 1

HCID 68577980N-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]methyl}pyridin-2-amineYield 55.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

1-[4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]methanamine (3.65 g, 11.4 mmol), 2-bromopyridine (910 μl, 9.48 mmol), tris(dibenzylideneacetone)dipalladium(0) (471 mg, 0.455 mmol), 2,2′-bis(diphenylphosphino)1,1′-binaphyl (567 mg, 0.910 mmol) and sodium tert-butoxide (1.29 g, 13.0 mmol) were stirred in toluene (50 ml) at 70° C. under nitrogen for 24 hours. The toluene was removed in vacuo and the residue partitioned between dichloromethane (50 ml) and saturated sodium bicarbonate solution (50 ml). The organic layer was separated and dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with ether:pentane (80:20 by volume) to provide the title compound (2.10 g, 46%) as a yellow solid. LRMS APCI+ m/z 399 [MH]+.

Workup

  1. customThe toluene was removed in vacuo
  2. customthe residue partitioned between dichloromethane (50 ml) and saturated sodium bicarbonate solution (50 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel eluting with ether:pentane (80:20 by volume)

Sources & evidence

ORD record
ord-f77a96f04f6c43898c8409ce951cabe9
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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