Diethyl Ether → 5-Bromo-3-[(trimethylsilyl)ethynyl]pyridin-2-amine

HRID 509544Notes

Reaction equation

HRID 509544 reaction equation
[NH2:1][C:2]1[C:7](I)=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.CCN(CC)CC.[Si:17]([C:21]#[CH:22])([CH3:20])([CH3:19])[CH3:18].CCOCC>C1COCC1.C(Cl)Cl.[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>[Br:9][C:5]1[CH:6]=[C:7]([C:22]#[C:21][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:2]([NH2:1])=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 15165082-Amino-5-bromo-3-iodopyridine

Product 1

HCID 167438055-Bromo-3-[(trimethylsilyl)ethynyl]pyridin-2-amineYield 84.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-amino-5-bromo-3-iodopyridine (105.28 g, 0.3522 mol), CuI (0.6708 g, 3.522 mmol) and PdCl2(PPh3)2 (2.472 g, 3.522 mmol) were dissolved in dry THF (210 mL) and degassed (vacuum/nitrogen cycles×4). Et3N (107.0 g, 0.1474 L, 1.057 mol) and TMS-acetylene (44.97 g, 0.06471 L, 0.4579 mol) were added and the resultant mixture was stirred at ambient temperature for 1¼ hours. The reaction was cooled in an ice-bath and ether (210 mL) was added. The resultant mixture was stirred at 0° C. for ½ hour, filtered through celite and the celite was washed copiously with ether. The filtrate was concentrated under reduced pressure to give a brown/black solid which was redissolved in the minimum necessary DCM and purified by column chromatography (eluting with DCM). The product containing fractions were concentrated in vacuo and the residue recrystallised from cyclohexane. The precipitate was isolated by filtration to give the sub-title compound as a white powder (80.25 g, 84% Yield). Analytical data identical to that of commercially available compound.

Workup

  1. customdegassed (vacuum/nitrogen cycles×4)
  2. temperatureThe reaction was cooled in an ice-bath
  3. filtrationfiltered through celite
  4. washthe celite was washed copiously with ether
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto give a brown/black solid which
  7. custompurified by column chromatography (eluting with DCM)
  8. additionThe product containing fractions
  9. concentrationwere concentrated in vacuo
  10. customthe residue recrystallised from cyclohexane
  11. customThe precipitate was isolated by filtration

Sources & evidence

ORD record
ord-9fa5fbc768e04607a520d9a7b477a1fb
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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