2-Bromo-4-methylpyridine → tert-Butyl 7-(4-methyl-2-pyridyl)-2,7-diazaspiro[4.5]decane-2-carboxylate

HRID 631820Notes

Reaction equation

HRID 631820 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[CH2:9]1[C:13]2([CH2:18][CH2:17][CH2:16][NH:15][CH2:14]2)[CH2:12][N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10]1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.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]>[CH3:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:15]2[CH2:16][CH2:17][CH2:18][C:13]3([CH2:12][N:11]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:10][CH2:9]3)[CH2:14]2)[CH:7]=1

Participants

8

Reactant 4

HCID 27340872-Bromo-4-methylpyridine2×HCID 23676156Sodium t-butoxideHCID 25112535BrettphosHCID 45934304tert-Butyl 2,7-diazaspiro[4.5]decane-2-carboxylate

Product 1

HCID 131735428tert-Butyl 7-(4-methyl-2-pyridyl)-2,7-diazaspiro[4.5]decane-2-carboxylate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

2-Bromo-4-methylpyridine (172 mg, 1 mmol) and tert-butyl 3,7-diazaspiro[4.5]decane-3-carboxylate (1 mmol, 240 mg) were dissolved in anhydrous dioxane (5 ml) under argon. Pd2(dba)3 (0.0165 mmol, 15 mg), Brettphos (30 mg, 0.0495 mmol), and sodium tert-butoxide (80 mg, 0.83 mmol) were added and the mixture was stirred at 100° C. overnight. Additional 2-bromo-4-methylpyridine (0.9 mmol, 100 μl) was added and stirring was continued at 100° C. overnight. The mixture was diluted with ethyl acetate, filtered through a plug of silica and concentrated under reduced pressure. The residue was purified by column chromatography (silica, gradient of 0 to 20% ethyl acetate in DCM) to yield 50 mg (0.15 mmol, 15%) MS(ESI) m/z=332.2 [M+1]+.

Workup

  1. stirringstirring
  2. waitwas continued at 100° C. overnight
  3. filtrationfiltered through a plug of silica
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (silica, gradient of 0 to 20% ethyl acetate in DCM)
  6. customto yield 50 mg (0.15 mmol, 15%) MS(ESI) m/z=332.2 [M+1]+

Sources & evidence

ORD record
ord-74a2739f5d3c41d8aef6bcd972023ff6
Source dataset
uspto-grants-2016_04
Patent number
US09321724B2

Reaction notes

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