2-Methyl-2-butene → 6-Butoxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid

HRID 1833152Notes

Reaction equation

HRID 1833152 reaction equation
[CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[C:12]([C:18](=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)=[N:11][CH:10]=[C:9]2[CH:28]=[O:29])[CH2:2][CH2:3][CH3:4].O.P([O-])(O)(O)=[O:32].[Na+].CC(=CC)C.Cl([O-])=O.[Na+]>C(O)(C)(C)C.O.CCCCCC>[CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[C:12]([C:18](=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)=[N:11][CH:10]=[C:9]2[C:28]([OH:32])=[O:29])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 220482916-Butoxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbaldehydeHCID 23668197Sodium Chlorite

Product 1

HCID 113043966-Butoxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acidYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8058HexaneSolvent

Procedure

To a stirred solution of afforded 6-butoxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbaldehyde (131 mg, 0.33 mmol) in t-butanol (2 mL) and water (2 mL) solution was added sodium dihydrogenphosphate monohydrate (184 mg, 1.33 mmol), 2-methyl-2-butene (0.226 mL, 2.00 mmol) and sodium chlorite (181 mg, 2.00 mmol) at room temperature. The reaction suspension was then stirred at room temperature for 14 hrs. The resulting two-phase mixture was partitioned between dichlormethane and water and acidified to pH=3 by addition of acetic acid. The aqueous phase was then extracted with dichloromethane (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (30 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a brown semi-solid oil. The crude product was recrystallized in ethyl acetate and hexane to afford 6-butoxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid (35 mg, 62% yield) as a light yellow solid. HR-MS m/e calcd for C26H21N1O6 (M−H+) 444.1442, found 444.1442; 1H NMR (300 MHz) compatible.

Workup

  1. customThe resulting two-phase mixture was partitioned between dichlormethane and water
  2. additionacidified to pH=3 by addition of acetic acid
  3. extractionThe aqueous phase was then extracted with dichloromethane (3×20 mL)
  4. washThe combined extracts were washed with saturated aqueous sodium chloride solution (30 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a brown semi-solid oil
  9. customThe crude product was recrystallized in ethyl acetate

Sources & evidence

ORD record
ord-a0a8d8588d85482c8ff32c5cce6f8f07
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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