Propyne → 4-(Tert-butyl-diphenyl-silanyloxymethyl)-2-prop-1-ynyl-pyridine

HRID 216657

Reaction equation

HRID 216657 reaction equation
[C:1]([SiH2:5][O:6][C:7]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][N:11]=[C:10](Cl)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[C:27]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:32]=CC=C[CH:28]=1.C(NCC)C.C#CC.C([O-])(O)=O.[Na+]>[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd+2].[Cu]I.CN(C)C=O>[C:1]([SiH2:5][O:6][C:7]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:28]#[C:27][CH3:32])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 6335PropyneHCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 1317297514-(Tert-butyl-diphenyl-silanyloxymethyl)-2-chloro-pyridine

Product 1

HCID 1317297504-(Tert-butyl-diphenyl-silanyloxymethyl)-2-prop-1-ynyl-pyridineYield 104.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 84124Bis(triphenylphosphine)palladium chlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A reaction tube is charged under an atmosphere of argon with 4-(tert-butyl-diphenyl-silanyloxymethyl)-2-chloro-pyridine (9.47 g, 24.79 mmol), palladium(II)-bis(triphenylphosphine)-dichloride (1.78 g, 2.49 mmol, 0.1 equiv), copper(I) iodide (477 mg, 2.49 mmol, 0.1 equiv), and triphenylphosphine (3.94 g, 14.9 mmol, 0.6 equiv). The tube is degassed by alternating three times between vacuum and argon. Diethylamine (39 ml) and N,N-dimethylformamide (2.0 ml), and propyne (50% in THF, 10.1 g, 247 mmol, 10 equiv) are added under an argon atmosphere. The tube is sealed, and the reaction mixture is heated under microwave irradiation for 20 minutes at 120° C. After cooling, the reaction mixture is poured into a semi-concentrated aqueous solution of NaHCO3. After three extractions with EtOAc, the combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (gradient from hexane/EtOAc 100:0 to 50:50) affords the title compound (6.0 g, 63%). 1H NMR (400 MHz, d6-DMSO): δ=8.41 (d, J=5.0 Hz, 1H), 7.57-7.55 (m, 4H), 7.43-7.32 (m, 11H), 7.27 (d, J=5.0 Hz, 1H), 4.72 (s, 2H), 1.99 (s, 3H), 0.98 (s, 9H). MS (ES+): 386 (M+H)+.

Workup

  1. customThe tube is degassed
  2. customThe tube is sealed
  3. temperatureAfter cooling
  4. extractionAfter three extractions with EtOAc
  5. washthe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via flash chromatography (gradient from hexane/EtOAc 100:0 to 50:50)

Sources & evidence

ORD record
ord-bc6e4e11056541b791e25ed4147f8dbd
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Linked notes

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