Water → 3-[(2E)-3-(4-tert-butylphenyl)-3-(5-chloro-6-methoxypyridin-2-yl)prop-2-en-1-yl]-1-methylpyrrolidin-2-one

HRID 70704Notes

Reaction equation

HRID 70704 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=[O:7].C([N-]C(C)C)(C)C.[Li+].Br[CH2:17]/[CH:18]=[C:19](/[C:30]1[N:35]=[C:34]([O:36][CH3:37])[C:33]([Cl:38])=[CH:32][CH:31]=1)\[C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=1.O>O1CCCC1>[C:26]([C:23]1[CH:22]=[CH:21][C:20](/[C:19](/[C:30]2[CH:31]=[CH:32][C:33]([Cl:38])=[C:34]([O:36][CH3:37])[N:35]=2)=[CH:18]\[CH2:17][CH:4]2[CH2:5][CH2:6][N:2]([CH3:1])[C:3]2=[O:7])=[CH:25][CH:24]=1)([CH3:27])([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 2724682Lithium diisopropylamideHCID 584528146-[(1E)-3-Bromo-1-(4-tert-butylphenyl)prop-1-en-1-yl]-3-chloro-2-methoxypyridine

Product 1

HCID 673992843-[(2E)-3-(4-tert-butylphenyl)-3-(5-chloro-6-methoxypyridin-2-yl)prop-2-en-1-yl]-1-methylpyrrolidin-2-oneYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-methylpyrrolidone (0.7 mL) in tetrahydrofuran (3 mL) was stirred at −78° C. in a nitrogen atmosphere, during which a lithium diisopropylamide solution (2.2 M, 0.5 mL) was added dropwise thereto. The mixture was stirred at the same temperature for 30 minutes. A solution of 6-[(1E)-3-bromo-1-(4-tert-butylphenyl)prop-1-en-1-yl]-3-chloro-2-methoxypyridine (182 mg) in tetrahydrofuran (2 mL) was slowly added dropwise thereto, and the mixture was stirred at −78° C. for one hour. Water was added to the reaction solution, which was then warmed to room temperature and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:10) to give 3-[(2E)-3-(4-tert-butylphenyl)-3-(5-chloro-6-methoxypyridin-2-yl)prop-2-en-1-yl]-1-methylpyrrolidin-2-one as a colorless oil (176 mg, 93%).

Workup

  1. additionwas added dropwise
  2. stirringthe mixture was stirred at −78° C. for one hour
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customafter which the solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:10)

Sources & evidence

ORD record
ord-604d621b3c7346c0a1b1491d543ea083
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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