Trimethylsilylacetylene → HCID 15822876, compound

HRID 1455200Notes

Reaction equation

HRID 1455200 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[Si:11]([C:15]#[CH:16])([CH3:14])([CH3:13])[CH3:12]>[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([C:16]#[C:15][Si:11]([CH3:14])([CH3:13])[CH3:12])=[N:3][CH:4]=1)([O-:10])=[O:9]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 782402-Bromo-5-nitropyridine

Product 1

HCID 15822876HCID 15822876, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

Alternatively, 2-bromo-5-nitro-pyridine (1.22 g, 6.0 mmoles), TMS-acetylene (0.9 mL, 6.4 mmoles), CuI (11 mg, 0.06 mmoles) and dichlorobis(triphenylphosphine)palladium (II) (210 mg, 0.3 mmoles) were combined and flushed with dry nitrogen for 10 min. After this period the mix was solubilized with 24 mL of anhydrous triethylamine (degassed), and the mix was stirred at ambient temperature for 4 hours. After this period the reaction mix was evaporated in vacuo and purified directly using flash silica chromatography (0-10% EtOAc/Hexane) to yield 5-nitro-2-trimethylsilanylethynyl-pyridine as a brown solid. This material was dissolved into THF (10 mL) and to this solution was added 100 mg of TFAB (on silica gel, 1.0-1.5 mmole F/g resin). The solution was stirred at ambient temperature for 15 min. After this period the reaction mix was evaporated in vacuo purified directly using flash silica chromatography (0-20% EtOAc/Hexane) to yield 2-ethynyl-5-nitro-pyridine as a clear liquid. This product was combined with 10% Pd/C (90 mg) and ethanol (20 ml) and was flushed with dry nitrogen. After oxygen exclusion the stirring mix was flushed with H2 and stirred under H2 pressure (balloon) for 16 hours. After this period the reaction mixture was flushed with nitrogen and then filtered through Celite. The filtrate was evaporated in vacuo and purified using flash silica chromatography (0-10% MeOH/DCM w/0.1% diethylamine) to yield 6-ethyl-pyridin-3-ylamine (442 mg, 60%—3 steps) as a brownish residue. 1H-NMR (CDCl3): δ 8.05-8.02 (m, 1H), 6.96-6.93 (m, 2H), 3.55 (br s, 2H), 2.71 (q, J=7.3 Hz, 2H), 1.25 (t, J=7.3 Hz, 3H).

Workup

  1. customflushed with dry nitrogen for 10 min
  2. waitAfter this period the mix was solubilized with 24 mL of anhydrous triethylamine (degassed)
  3. additionAfter this period the reaction mix
  4. customwas evaporated in vacuo
  5. custompurified directly

Sources & evidence

ORD record
ord-651d617ea38e466a9b8296a155892a89
Source dataset
uspto-grants-2009_01
Patent number
US07482366B2

Reaction notes

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