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

HRID 434163Notes

Reaction equation

HRID 434163 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-pyridine

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a cooled 5° C., stirred slurry of methyltriphenylphosphonium bromide (75.7 grams) in tetrahydrofuran (530 mL) was added potassium t-butoxide (23.8 grams) portionwise over a 5 minute period to produce a yellow slurry. After 30 minutes, 2-chloro-5-formylpyridine (25.0 grams) was added in one portion to produce a purple colored slurry. After an additional 30 minutes, 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 minutes, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting semi-solid was stirred for 30 minutes 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 grams of silica gel and chromatographed over 700 grams of silica gel eluting with a gradient of ethyl acetate(0-8%)/hexanes to afford the title compound as a colorless oil, 15.2 grams 1H NMR (400 MHz, CDCl3): δ=8.35 (s, 1H); 7.69(d, 1H); 6.65 (dd, 1H); 5.79 (d, 1H); 5.40 (d, 1H).

Workup

  1. customto produce a yellow slurry
  2. customto produce a purple colored slurry
  3. waitAfter an additional 30 minutes
  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 minutes 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 grams of silica gel
  13. customchromatographed over 700 grams of silica gel eluting with a gradient of ethyl acetate(0-8%)/hexanes

Sources & evidence

ORD record
ord-4b4122c0db234cde9b918a2cd5e7f727
Source dataset
uspto-grants-2003_12
Patent number
US06670480B2

Reaction notes

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