tert-Butyl 4-ethynylpiperidine-1-carboxylate → HCID 90412447, compound

HRID 1522009Notes

Reaction equation

HRID 1522009 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[C:3]=1I.[C:17]([CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)#[CH:18]>O1CCCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[C:3]=1[C:18]#[C:17][CH:19]1[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]1

Participants

6

Reactant 2

HCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 50986342N-(4-Chloro-5-fluoro-3-iodo-2-pyridinyl)-2,2-dimethylpropanamide

Product 1

HCID 90412447HCID 90412447, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of N-(4-chloro-5-fluoro-3-iodopyridin-2-yl)pivalamide (1 g, 2.80 mmol), tert-butyl 4-ethynylpiperidine-1-carboxylate (0.880 g, 4.21 mmol), copper(I) iodide (0.053 g, 0.28 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.197 g, 0.280 mmol) in 50 mL tetrahydrofuran was degassed with nitrogen. The mixture was stirred at room temperature for 48 hours and at 50° C. for 8 hours. The mixture was filtered and the filtrate was diluted with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica-gel column chromatography eluting with 0-40% ethyl acetate in heptane to afford the title compound. MS (ESI(+)) m/e 438 (M+H)+.

Workup

  1. customwas degassed with nitrogen
  2. filtrationThe mixture was filtered
  3. additionthe filtrate was diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica-gel column chromatography
  10. washeluting with 0-40% ethyl acetate in heptane

Sources & evidence

ORD record
ord-ea94053a09f0406daa704c6c4ae74882
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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