1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 5-(4-((t-Butyldimethylsilyloxy)methyl)piperidin-1-yl)-2-chloropyridine

HRID 876000

Reaction equation

HRID 876000 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[Si:9]([O:16][CH2:17][CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C(OCC)(=O)C.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:9]([O:16][CH2:17][CH:18]1[CH2:19][CH2:20][N:21]([C:2]2[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=2)[CH2:22][CH2:23]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]

Participants

8

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27344145-Bromo-2-chloropyridineHCID 23676156Sodium t-butoxideHCID 670219944-{[(Tert-butyldimethylsilyl)oxy]methyl}piperidine

Product 1

HCID 582995615-(4-((t-Butyldimethylsilyloxy)methyl)piperidin-1-yl)-2-chloropyridineYield 9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-2-chloropyridine (1.00 g, 5.20 mmol), 4-((t-butyldimethylsilyloxy)-methyl)piperidine (284), (1.19 g, 5.20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0952 g, 0.104 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.180 g, 0.312 mmol), and sodium t-butoxide (0.749 g, 7.79 mmol) were dissolved in 40 mL dioxane under argon. The reaction was heated at 80° C. for 17 hours. The resulting solution was cooled an taken up in ethyl acetate (125 mL) and washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate) afforded compound 281 as a white solid (158 mg, 9%).

Workup

  1. temperatureThe resulting solution was cooled
  2. washwashed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. customto give an orange oil
  6. washSilica gel chromatography (gradient elution hexanes/0-10% ethyl acetate)

Sources & evidence

ORD record
ord-28edc2b091c242b9b9d7501774b6b931
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Linked notes

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