Tetrahydrofuran → Tert-butyl 4-(6-{2-[4-(hydroxymethyl)phenyl]vinyl}pyridin-3-yl)piperazine-1-carboxylate

HRID 1465471Notes

Reaction equation

HRID 1465471 reaction equation
[Cl-].[OH:2][CH2:3][C:4]1[CH:29]=[CH:28][C:7]([CH2:8][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:6][CH:5]=1.[CH:30]([C:32]1[N:37]=[CH:36][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]2)=[CH:34][CH:33]=1)=O.O1CCCC1.CC(C)([O-])C.[K+]>O>[OH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH:8]=[CH:30][C:32]2[N:37]=[CH:36][C:35]([N:38]3[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]3)=[CH:34][CH:33]=2)=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 23447282[4-(Hydroxymethyl)benzyl](triphenyl)phosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 58181229tert-Butyl 4-(6-formylpyridin-3-yl)piperazine-1-carboxylate

Product 1

HCID 67030232Tert-butyl 4-(6-{2-[4-(hydroxymethyl)phenyl]vinyl}pyridin-3-yl)piperazine-1-carboxylateYield 71.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of [4-(hydroxymethyl)benzyl](triphenyl)phosphonium chloride (1.283 g, 3.064 mmol), tert-butyl 4-(6-formylpyridin-3-yl)piperazine-1-carboxylate (876.3 mg, 3.008 mmol) and anhydrous tetrahydrofuran (10 ml) was added potassium tert-butoxide (383.9 mg, 3.421 mmol), and the mixture was stirred at room temperature for 1 hr. Water (20 ml) was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The combined organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1). The fraction containing the target product was concentrated and the obtained solid was dissolved in ethyl acetate, and extracted twice with 0.2M hydrochloric acid. The aqueous layer was saturated with sodium carbonate, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl 4-(6-{2-[4-(hydroxymethyl)phenyl]vinyl}pyridin-3-yl)piperazine-1-carboxylate (850.2 mg, yield 71.5%, E/Z mixture) as a pale-yellow solid.

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1)
  5. additionThe fraction containing the target product
  6. concentrationwas concentrated
  7. dissolutionthe obtained solid was dissolved in ethyl acetate
  8. extractionextracted twice with 0.2M hydrochloric acid
  9. extractionthe mixture was extracted with ethyl acetate
  10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2b25cbb4f8e74c6a8f2638aa94672490
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

Loading…