Tetrahydrofuran → 6-tert-Butyl-2-chloro-3-vinylpyridine

HRID 1438398Notes

Reaction equation

HRID 1438398 reaction equation
[CH2:1]1COCC1.C([Li])CCC.[C:11]([C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[C:17]([Cl:23])[N:16]=1)([CH3:14])([CH3:13])[CH3:12]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC>[C:11]([C:15]1[N:16]=[C:17]([Cl:23])[C:18]([CH:19]=[CH2:1])=[CH:21][CH:22]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 838189586-Tert-butyl-2-chloronicotinaldehydeHCID 178418339Butyllithium

Product 1

HCID 866390506-tert-Butyl-2-chloro-3-vinylpyridineYield 71%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8058HexaneSolvent

Procedure

To a diethyl ether (17 ml) solution of 6-tert-butyl-2-chloronicotinonitrile (Tetrahedron 1965, 21, 2453-2467, 1.0 g, 5.4 mmol) was added 0.94 M diisobutylaluminum hydride in toluene solution (8.6 ml, 8.0 mmol) at −78° C. and the reaction was allowed to warm to room temperature over 2 hours with stirring. Then the reaction was quenched with 10% potassium sodium tartrate tetrahydrate aqueous solution and the whole was extracted with EtOAc, and washed with 2M sodium hydroxide aqueous solution and brine. The organic layer was evaporated and purified by silica gel column chromatography, eluting with hexane/EtOAc (5:1), to give 6-tert-butyl-2-chloronicotinaldehyde (1.0 g, 95%). To a THF (24 ml) suspension of methyltriphenylphosphonium bromide (5.3 g, 14.8 mmol) was added 1.60 M n-butyllithium (9.3 ml, 14.8 mmol) in hexane solution at 0° C. and the reaction was stirred for 30 minutes. Then to this mixture was added a THF (5 ml) solution of the 6-tert-butyl-2-chloronicotinaldehyde (1.0 g, 5.2 mmol) at 0° C., and the reaction was stirred for 2 hours at room temperature. The reaction was quenched with saturated ammonium chloride aqueous solution, and the whole was extracted with EtOAc, and dried over magnesium sulfate. The organic layer was evaporated and purified by silica gel column chromatography, eluting with hexane/EtOAc (10:1), to give the title compound (735 mg, 71%).

Workup

  1. stirringthe reaction was stirred for 2 hours at room temperature
  2. customThe reaction was quenched with saturated ammonium chloride aqueous solution
  3. extractionthe whole was extracted with EtOAc
  4. dry with materialdried over magnesium sulfate
  5. customThe organic layer was evaporated
  6. custompurified by silica gel column chromatography
  7. washeluting with hexane/EtOAc (10:1)

Sources & evidence

ORD record
ord-45e89e06b5404e0ab2ba5827d1d94c4f
Source dataset
uspto-grants-2009_11
Patent number
US07622589B2

Reaction notes

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