2-Methyl-2-butene → 4-Methoxy-5-(3-methoxy-propoxy)-2-methyl-benzoic acid

HRID 1158458

Reaction equation

HRID 1158458 reaction equation
[CH3:1][O:2][C:3]1[C:10]([O:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:9][C:6]([CH:7]=[O:8])=[C:5]([CH3:17])[CH:4]=1.C([OH:22])(C)(C)C.C(Cl)Cl.CC(=CC)C.[O-]Cl=O.[Na+]>O.CCOCC>[CH3:1][O:2][C:3]1[C:10]([O:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:9][C:6]([C:7]([OH:22])=[O:8])=[C:5]([CH3:17])[CH:4]=1

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 18914702t-Butanol dichloromethaneHCID 23668197Sodium ChloriteHCID 592239044-Methoxy-5-(3-methoxy-propoxy)-2-methyl-benzaldehyde

Product 1

HCID 595123794-Methoxy-5-(3-methoxy-propoxy)-2-methyl-benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 4-methoxy-5-(3-methoxy-propoxy)-2-methyl-benzaldehyde (1.25 g, 5.25 mmol) in a 3:1 mixture of tert-butanol/CH2Cl2 (60 mL) is added 2-methyl-2-butene (25.0 mL), followed by dropwise addition of a solution of NaClO2 (5.81 g, 51.4 mmol) and NaH2PO4 (4.07 g, 33.6 mmol) in water (45 mL) over 15 min at room temperature, and stirring is continued overnight. The reaction mixture is poured into ice/saturated aqueous NaHCO3 solution, the water phase is washed with AcOEt, then acidified and extracted with AcOEt. The combined organics are washed with brine, dried (Na2SO4) and concentrated to give a yellow solid. The crude product is stirred for 30 min in a 95:5 mixture of hexaneldiisopropyl ether (25 mL), the precipitate is filtered off, washed with a 95:5 mixture of hexane/diisopropyl ether and dried to give the title compound as yellowish solid. MS: 253.0 [M−H]+. tR (HPLC, Nucleosil C18HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.23 min. 1H-NMR (CDCl3): δ 1.96 (m, 2H), 2.51 (s, 3H), 3.27 (s, 3H), 3.48 (m, 2H), 3.84 (s, 3H), 4.00 (m, 2H), 6.89 (s, 1H), 7.41 (s, 1H) ppm.

Workup

  1. additionThe reaction mixture is poured into ice/saturated aqueous NaHCO3 solution
  2. washthe water phase is washed with AcOEt
  3. extractionextracted with AcOEt
  4. washThe combined organics are washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto give a yellow solid
  8. filtrationthe precipitate is filtered off
  9. washwashed with a 95:5 mixture of hexane/diisopropyl ether
  10. customdried

Sources & evidence

ORD record
ord-62cccaaf728244f1bdc659ab9e5fb907
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Linked notes

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