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

HRID 1833162Notes

Reaction equation

HRID 1833162 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][C:16]=2[O:17][CH3:18])[C:13]([C:19](=[O:28])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=2)=[N:12][CH:11]=[C:10]3[CH:29]=[O:30])[CH2:5][CH2:4][CH2:3][CH2:2]1.O.P([O-])(O)(O)=[O:33].[Na+].CC(=CC)C.Cl([O-])=O.[Na+]>C(O)(C)(C)C.O.CCCCCC>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][C:16]=2[O:17][CH3:18])[C:13]([C:19](=[O:28])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=2)=[N:12][CH:11]=[C:10]3[C:29]([OH:33])=[O:30])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 220483816-Cyclopentyloxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbaldehydeHCID 23668197Sodium Chlorite

Product 1

HCID 220482616-Cyclopentyloxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acidYield 58.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8058HexaneSolvent

Procedure

To a stirred solution of afforded 6-cyclopentyloxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbaldehyde (200 mg, 0.49 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 dichloromethane 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-cyclopentyloxy-7-methoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid (120 mg, 58% yield) as a yellow solid: HR-MS m/e calcd for C24H23N1O6 (M−H+) 421.1525, found 421.1526; 1H NMR (300 MHz) compatible.

Workup

  1. customThe resulting two-phase mixture was partitioned between dichloromethane 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-2b3c1a6ffd22449c884ebc40a409548a
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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