3,3-Dimethyl-1-butyne → 2-(6-Chloro-4-(3,3-dimethylbut-1-ynyl)pyridin-3-ylamino)ethanol

HRID 1044021Notes

Reaction equation

HRID 1044021 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][OH:11])=[C:4](I)[CH:3]=1.[CH3:13][C:14]([CH3:18])([CH3:17])[C:15]#[CH:16]>CCN(CC)CC.[Cu]I>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][OH:11])=[C:4]([C:16]#[C:15][C:14]([CH3:18])([CH3:17])[CH3:13])[CH:3]=1

Participants

5

Reactant 2

HCID 135123,3-Dimethyl-1-butyneHCID 579081632-(6-Chloro-4-iodopyridin-3-ylamino)ethanol

Product 1

HCID 579081822-(6-Chloro-4-(3,3-dimethylbut-1-ynyl)pyridin-3-ylamino)ethanolYield 29.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-(6-chloro-4-iodopyridin-3-ylamino)ethanol (14.5 g, 49 mmol) in Et3N (200 mL) were added 3,3-dimethyl-but-1-yne (12.0 g, 146 mol), CuI (0.9 g, 4.9 mmol) and Pd(PPh3)Cl2 (3.4 g, 4.9 mmol) under N2 atmosphere. The mixture was refluxed overnight and quenched with H2O (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and purified by chromatography on silica gel (3% ethyl acetate in petroleum ether as eluant) to afford 2-(6-chloro-4-(3,3-dimethylbut-1-ynyl)pyridin-3-ylamino)ethanol (3.6 g, 29%). 1H-NMR (CDCl3, 300 MHz) δ 7.74 (s, 1H), 7.11 (s, 1H), 4.77 (br s, 1H), 3.92-3.90 (m, 2H), 3.78-3.36 (m, 2H), 1.34 (s, 9H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customquenched with H2O (100 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. custompurified by chromatography on silica gel (3% ethyl acetate in petroleum ether as eluant)

Sources & evidence

ORD record
ord-9e626c80d7304b5597a20f0ce4ef1311
Source dataset
uspto-grants-2013_10
Patent number
US08563573B2

Reaction notes

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