Lithium Hydroxide → 3-Methyl-4-(morpholin-4-yl)benzoic acid

HRID 219785Notes

Reaction equation

HRID 219785 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[C:5]([O:7]C)=[O:6].[OH-].[Li+]>C1COCC1.O>[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[N:12]1[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1)[C:5]([OH:7])=[O:6]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 67528858Methyl 3-methyl-4-morpholin-4-ylbenzoate

Product 1

HCID 184757233-Methyl-4-(morpholin-4-yl)benzoic acidYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of methyl 3-methyl-4-morpholin-4-ylbenzoate obtained in step 1 (4 g, 169.3 mmol) in THF (100 mL) and water (5 mL) was added lithium hydroxide (2 g, 84.6 mol). The resulting mixture was heated at 50° C. for 12 h. Solvents were removed under vacuum and the resulting mass was diluted with water. The aqueous layer was washed with DCM (2×50 mL) and was acidified with conc HCl (pH=4). It was extracted with EtOAc (2×100 mL). The EtOAc layer was washed with brine and dried over sodium sulfate, affording the title compound as a yellow solid (3.6 g, 97%). 1H NMR (DMSO-d6, 400 MHz) δ 12.5 (bs, 1H), 7.72-7.74 (m, 2H), 7.04-7.06 (m, 1H), 3.72-3.75 (m, 4H), 2.88-2.90 (m, 4H), 2.33 (s, 3H). LC/MS (Method A): 222.1 (M+H)+. HPLC (Method B) Rt 1.42 min (Purity: 98.3%).

Workup

  1. customSolvents were removed under vacuum
  2. additionthe resulting mass was diluted with water
  3. washThe aqueous layer was washed with DCM (2×50 mL)
  4. extractionIt was extracted with EtOAc (2×100 mL)
  5. washThe EtOAc layer was washed with brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-97bddb825b5f448885d1693d89aa62b4
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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