Lithium Hydroxide → 4-Cyclopropyl-2-methylbenzoic acid

HRID 970643Notes

Reaction equation

HRID 970643 reaction equation
[OH-].[Li+].[CH:3]1([C:6]2[CH:15]=[CH:14][C:9]([C:10]([O:12]C)=[O:11])=[C:8]([CH3:16])[CH:7]=2)[CH2:5][CH2:4]1>O.C1COCC1.CO>[CH:3]1([C:6]2[CH:15]=[CH:14][C:9]([C:10]([OH:12])=[O:11])=[C:8]([CH3:16])[CH:7]=2)[CH2:4][CH2:5]1

Participants

6

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 59020660Methyl 4-cyclopropyl-2-methylbenzoate

Product 1

HCID 590206584-Cyclopropyl-2-methylbenzoic acidYield 95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of lithium hydroxide (90 mg, 1.97 mmol) in H2O (1 mL) was added in one portion to a stirred solution of methyl 4-cyclopropyl-2-methylbenzoate (125 mg, 0.66 mmol) in THF (2 mL) and MeOH (2 mL). The mixture was stirred at room temperature for 30 min then at 50° C. for 2 hours. A further aliquot of lithium hydroxide (90 mg) in H2O (1 mL) and MeOH (1 mL) was added, and the mixture was stirred at 50° C. overnight. The organics were removed under vacuum and H2O (20 mL) was added. The mixture was adjusted to pH 4-5 by the use of 1N HCl (a precipitate emerges) and then extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered and the filtrate concentrated under vacuum to give the product (110 mg, 95%) as a solid. 1H NMR (CDCl3; 400 MHz) δ 7.98 (1H, d), 6.96-6.92 (2H, m), 2.63 (3H, s), 1.94-1.87 (1H, m), 1.07-1.01 (2H, m), 0.80-0.76 (2H, m).

Workup

  1. waitat 50° C. for 2 hours
  2. stirringthe mixture was stirred at 50° C. overnight
  3. customThe organics were removed under vacuum and H2O (20 mL)
  4. additionwas added
  5. extractionthen extracted with EtOAc (2×20 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-a3d47c1510a040cca42420d496161798
Source dataset
uspto-grants-2007_12
Patent number
US07312233B2

Reaction notes

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