Hydrochloric Acid → (2E)-2-[(3-bromo-4-pyridyl)methylene]-6,7-dimethoxy-tetralin-1-one

HRID 2207184Notes

Reaction equation

HRID 2207184 reaction equation
N(C(C)C)C(C)C.[Li]CCCC.[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[O:25][CH3:26])[C:21](=[O:27])[CH2:20][CH2:19][CH2:18]2.[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1[CH:35]=O.Cl>C1COCC1>[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1/[CH:35]=[C:20]1/[C:21](=[O:27])[C:22]2[C:17]([CH2:18][CH2:19]/1)=[CH:16][C:15]([O:14][CH3:13])=[C:24]([O:25][CH3:26])[CH:23]=2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 2668163,4-Dihydro-6,7-dimethoxy-1(2H)-naphthalenoneHCID 27629973-Bromopyridine-4-carboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 118557935(2E)-2-[(3-bromo-4-pyridyl)methylene]-6,7-dimethoxy-tetralin-1-oneYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (i-Pr)2NH (0.3 mL, 2.2 mmol) at 0° C. in dry THF (15 mL) was added n-BuLi (1.22 M solution in hexane, 2.7 mL, 2.2 mmol), the mixture was stirred for 15 min at this temperature, after which the 6,7-dimethoxy-1-tetralone (0.412 g, 2 mmol) in dry THF (7 mL) was slowly added at −78° C. After 30 min at this temperature, 3-bromo-4-pyridinecarboxaldehyde (0.446 g, 2.4 mmol) in dry THF (7 mL) was slowly added and the solution was stirred for 30 min at −78° C. before allowed to reach room temperature and being stirred for a night. Then, the mixture was hydrolyzed by HCl 1N and extracted by AcOEt to eliminate the possible excess of tetralone. The aqueous layer was neutralized by NaHCO3 and the compound was extracted by CH2Cl2 three times. The combined organic layers were dried over MgSO4 and concentrated to dryness. The residue was purified by column chromatography on SiO2 (gradient of EtOAc in petroleum ether) to afford the expected product 84 (Yield 598.7 mg, 80%).

Workup

  1. stirringthe solution was stirred for 30 min at −78° C.
  2. customto reach room temperature
  3. stirringbeing stirred for a night
  4. extractionextracted by AcOEt
  5. extractionthe compound was extracted by CH2Cl2 three times
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by column chromatography on SiO2 (gradient of EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-26b44ab45e3c429298e8263e6932a818
Source dataset
uspto-grants-2016_06
Patent number
US09376387B2

Reaction notes

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