Diisopropylamine → 2,2-Dimethyl-5-[2-(4-pyridinyl)ethenyl]-3(2H)-furanone

HRID 1089511Notes

Reaction equation

HRID 1089511 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1([CH3:21])[C:18](=[O:19])[CH:17]=[C:16]([CH3:20])[O:15]1.[N:22]1[CH:27]=[CH:26][C:25]([CH:28]=O)=[CH:24][CH:23]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O1CCCC1.CCCCCC.C(N(CC)CC)C.CN(C)P(N(C)C)(N(C)C)=O>[CH3:13][C:14]1([CH3:21])[C:18](=[O:19])[CH:17]=[C:16]([CH:20]=[CH:28][C:25]2[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=2)[O:15]1

Participants

10

Reactant 5

HCID 7912DiisopropylamineHCID 9845Trifluoroacetic anhydrideHCID 133894-PyridinecarboxaldehydeHCID 1370803(2H)-Furanone, 2,2,5-trimethyl-HCID 178418339Butyllithium

Product 1

HCID 543140152,2-Dimethyl-5-[2-(4-pyridinyl)ethenyl]-3(2H)-furanoneYield 32%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of dry diisopropylamine (2.6 mL, 19.1 mM) in dry tetrahydrofuran (350 mL) at -78° C., was added dropwise a 2.5M solution of n-butyllithium in hexane (7.6 mL, 19.1 mM). After the reaction solution was stirred for 15 minutes, a solution of 2,2,5-trimethyl-3(2H)-furanone (20 g, 15.9 mM) in tetrahydrofuran (25 mL) was added dropwise. Hexamethylphosphoramide (6.4 mL, 35.7 mM) was then added after 30 minutes. Finally, 4-pyridinecarboxaldehyde (2.5 g, 23.5 mM) in tetrahydrofuran (25 mL) was added in one portion. The reaction solution was stirred 15 minutes when trifluoracetic anhydride (6.7 mL, 47.7 mM) was added in one portion. Again, the reaction solution was stirred 15 minutes before triethylamine (11 mL, 80 mM) was added and was allowed to warm to room temperature. The reaction mixture was concentrated to 100 mL then diluted with diethyl ether (300 mL). The organic layer was extracted with 1N aqueous hydrochloric acid (100 mL). The acid layer was neutralized with solid sodium bicarbonate and washed with diethyl ether (2×100 mL). The combined etheral layers were washed with saturated aqueous sodium chloride (2×50 mL), dried over MgSO 4, filtered and concentrated under reduced pressure to give a brown crystalline solid. The crude product was purified by chromatography (silica gel, pet. ether/ethyl acetate) to afford a yellow crystalline solid (935 mg, 32% yield), m.p. 94°-96° C.

Workup

  1. additionwas added in one portion
  2. additionwas added
  3. concentrationThe reaction mixture was concentrated to 100 mL
  4. additionthen diluted with diethyl ether (300 mL)
  5. extractionThe organic layer was extracted with 1N aqueous hydrochloric acid (100 mL)
  6. washwashed with diethyl ether (2×100 mL)
  7. washThe combined etheral layers were washed with saturated aqueous sodium chloride (2×50 mL)
  8. dry with materialdried over MgSO 4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a brown crystalline solid
  12. customThe crude product was purified by chromatography (silica gel, pet. ether/ethyl acetate)

Sources & evidence

ORD record
ord-9804a30f6cba43578d2a56a59b1e3a43
Source dataset
uspto-grants-1990_10
Patent number
US04966905

Reaction notes

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