Water → 3-(Ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid

HRID 1783232Notes

Reaction equation

HRID 1783232 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:14]([O:16]CC)=[O:15])[CH:6]=[C:7]([CH:13]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9].O.O.[OH-].[Li+]>C(O)C>[CH2:11]([O:10][C:8]([C:7]1[CH:6]=[C:5]([CH:4]=[C:3]([CH2:2][OH:1])[CH:13]=1)[C:14]([OH:16])=[O:15])=[O:9])[CH3:12]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 610139Diethyl 5-(hydroxymethyl)isophthalate

Product 1

HCID 210858293-(Ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of diethyl 1,3,5-benzenetricarboxylate (5.2 g) and borane methylsulfide complex (6.1 g) is stirred in THF (150 mL) at 20-25 degrees C. overnight. The mixture is then treated with methanol, concentrated to dryness, and chouromatographed (silica gel) to give diethyl 5-(hydroxymethyl)isophthalate. Diethyl 5-(hydroxymethyl)isophthalate (3.4 g) is hydroyzed in ethanol and water with lithium hydroxide monohydrate (0.57 g) at 20-25 degrees C. for 3.5 hours at which time the solvents are removed under reduced pressure. Water (100 mL) is added and the mixture is acidified to pH=4 with concentrated hydrochloric acid. The mixture is extracted with ethyl acetate and dried over magnesium sulfate, filtered, and concentrated to give 3-(ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid, high resolution MS MH+=225.0769. 3-(Ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid (2.3 g), EDC (3.0 g), 1-HOBT (2.1 g), diisopropylethylamine (2.7 mL), dipropyl amine (2.8 mL), and DMF (50 mL) are stirred at 20-25 degrees C. overnight. The mixture is then partitioned between ethyl acetate, water, and saline. The organic phase is separated and dried over magnesium sulfate, filtered, and concentrated. Chromatography (silica gel) gives ethyl 3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoate, NMR (CDCl3) δ 0.77, 1.0, 1.4, 1.6, 1.7, 3.2, 3.5, 4.4, 4.8, 7.6, 8.0 and 8.1.

Workup

  1. customat 20-25 degrees C
  2. customfor 3.5 hours at which time the solvents are removed under reduced pressure
  3. additionWater (100 mL) is added
  4. extractionThe mixture is extracted with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-628bf9c19d46473e8f9be5f1a7bed15e
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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