Isopropanol → 3-Isopropoxy-4-methoxybenzoic acid

HRID 1983572Notes

Reaction equation

HRID 1983572 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7]C)=[O:6].[CH:14](O)([CH3:16])[CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(OCC)(=O)C>[CH:14]([O:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([OH:7])=[O:6])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 4056967Methyl 3-hydroxy-4-methoxybenzoate

Product 1

HCID 27366803-Isopropoxy-4-methoxybenzoic acidYield 82%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of methyl 3-hydroxy-4-methoxybenzoate (3.00 g, 16.5 mmol), isopropanol (1.9 mL, 24.8 mmol) and triphenylphosphine (5.40 g, 20.6 mmol) in ethyl acetate (70 mL) was added, dropwise, diethyl azodicarboxylate (3.9 mL, 25 mmol). The reaction was allowed to proceed overnight and then washed with aqueous sodium bicarbonate solution, dried (sodium sulfate) and concentrated. The resulting yellow oil was taken up in 1:1:1 tetrahydrofuran/methanol/1 N aqueous sodium hydroxide (120 mL) and heated at reflux. After 4 hours additional 1 N aqueous sodium hydroxide (10 mL) was added and the mixture was stirred at room temperature overnight. The reaction was then concentrated to remove organic solvents and diluted with water. After washing several times with ethyl acetate, the solution was stirred and acidified with 1 N aqueous hydrochloric acid (50 mL). The resulting precipitate was filtered off, rinsed with water and vacuum oven dried to afford 2.83 g (82%) of product as a white solid: 1H NMR (DMSO-d6) δ 12.64 (s, 1H), 7.53 (dd, J=8.4, 1.8 Hz, 1H), 7.41 (d, J=1.8 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 4.55 (sept, J=6.0 Hz, 1H), 3.71 (s, 3H) ppm.

Workup

  1. washwashed with aqueous sodium bicarbonate solution
  2. dry with materialdried (sodium sulfate)
  3. concentrationconcentrated
  4. temperatureheated
  5. temperatureat reflux
  6. additionAfter 4 hours additional 1 N aqueous sodium hydroxide (10 mL) was added
  7. concentrationThe reaction was then concentrated
  8. customto remove organic solvents
  9. additiondiluted with water
  10. washAfter washing several times with ethyl acetate
  11. stirringthe solution was stirred
  12. filtrationThe resulting precipitate was filtered off
  13. washrinsed with water and vacuum oven
  14. customdried

Sources & evidence

ORD record
ord-8650c6f7e97e422c846302ae9f1b4f43
Source dataset
uspto-grants-2009_06
Patent number
US07541466B2

Reaction notes

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