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

HRID 14020Notes

Reaction equation

HRID 14020 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-6d3546c6cb8d47ff825c2d87f1e50534
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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