Ammonium Chloride → 2-Chloro-5-vinyl-pyridine

HRID 495713Notes

Reaction equation

HRID 495713 reaction equation
[CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][N:9]=1.[Cl-].[NH4+]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]=[CH2:1])=[CH:10][N:9]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 27640536-Chloropyridine-3-carbaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 118154432-Chloro-5-vinyl-pyridineYield 61.7%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a cooled (5° C.), stirred slurry of methyltriphenylphosphonium bromide (75.7 g) in tetrahydrofuran (530 mL) was added potassium t-butoxide (23.8 g) portionwise over a 5-min period to produce a yellow slurry. After 30 min, 2-chloro-5-formylpyridine (25.0 g) was added in one portion to produce a purple colored slurry. After an additional 30 min, the reaction mixture was treated with saturated aqueous ammonium chloride (200 mL) and a majority of the tetrahydrofuran was removed in vacuo. The resulting mixture was washed with ethyl acetate, the combined organic layers washed with saturated aqueous brine, stirred over activated charcoal for 20 min, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting semi-solid was stirred for 30 min with a solution of 2:1 diethyl ether/petroleum ether (375 mL), filtered and the solids washed with an additional portion of 2:1 diethyl ether/petroleum ether (300 mL). The combined filtrates were concentrated in vacuo, pre-loaded on 60 g of silica gel and chromatographed over 700 g of silica gel eluting with a gradient of ethyl acetate (0-8%)/hexanes to afford 15.2 g of the title compound (I-2b) as a colorless oil.

Workup

  1. customto produce a yellow slurry
  2. customto produce a purple colored slurry
  3. waitAfter an additional 30 min
  4. customa majority of the tetrahydrofuran was removed in vacuo
  5. washThe resulting mixture was washed with ethyl acetate
  6. washthe combined organic layers washed with saturated aqueous brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. stirringThe resulting semi-solid was stirred for 30 min with a solution of 2:1 diethyl ether/petroleum ether (375 mL)
  10. filtrationfiltered
  11. washthe solids washed with an additional portion of 2:1 diethyl ether/petroleum ether (300 mL)
  12. concentrationThe combined filtrates were concentrated in vacuo, pre-loaded on 60 g of silica gel
  13. customchromatographed over 700 g of silica gel eluting with a gradient of ethyl acetate (0-8%)/hexanes

Sources & evidence

ORD record
ord-0c614a127d8746e2aced87bf4aa2e94e
Source dataset
uspto-grants-2005_09
Patent number
US06939867B2

Reaction notes

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