Benzeneacetic acid, 3,4-dimethoxy-, methyl ester → HCID 68182212, compound

HRID 1620176Notes

Reaction equation

HRID 1620176 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl.Cl[CH2:28][C:29]1[CH:30]=[N:31][C:32]2[C:37]([CH:38]=1)=[C:36]([O:39][CH3:40])[CH:35]=[CH:34][CH:33]=2>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([CH2:28][C:29]2[CH:30]=[N:31][C:32]3[C:37]([CH:38]=2)=[C:36]([O:39][CH3:40])[CH:35]=[CH:34][CH:33]=3)[C:12]([O:14][CH3:15])=[O:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 85213Benzeneacetic acid, 3,4-dimethoxy-, methyl ester2×HCID 2733832Lithium HexamethyldisilazideHCID 68182227HCID 68182227, compound2×

Product 1

HCID 68182212HCID 68182212, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(3,4-dimethoxyphenyl)acetate SLA 28134 (73 mg, 347 μmol) in dry THF (10 mL) at −66° C. in a 25 mL round-bottomed flask equipped with a magnetic stirrer was added LiHMDS (1.0 N in TBME, 0.70 mL, 700 μmol) and the mixture was stirred for 20 min at that temperature. 3-(Chloromethyl)-5-methoxyquinoline hydrochloride CCH 34144B (84 mg, 344 μmol) was then added and the mixture was stirred for 2 h allowing the temperature to reach RT. The mixture was then quenched by carefully adding H2O (4 mL) and diluted with EtOAc (30 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (40 mL). Both organic phases were washed with brine (10 mL), then combined, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50) provided methyl 2-(3,4-dimethoxyphenyl)-3-(5-methoxyquinolin-3-yl)propanoate 34144-5 as a pale yellow oil (46 mg, 35% yield).

Workup

  1. stirringthe mixture was stirred for 2 h
  2. customto reach RT
  3. customThe mixture was then quenched by carefully adding H2O (4 mL)
  4. additiondiluted with EtOAc (30 mL)
  5. customThe organic phase was isolated
  6. extractionthe aqueous phase was further extracted with CH2Cl2 (40 mL)
  7. washBoth organic phases were washed with brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated at 40° C. under vacuum
  11. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50)

Sources & evidence

ORD record
ord-5b9752fb0e7049b6bcb8aa3e74432a15
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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