Dimethyl 4-aminoisophthalate → Dimethyl-4-(2'-isopropoxybenzoylamino)-isophthalate

HRID 1413809Notes

Reaction equation

HRID 1413809 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1.[CH:16]([O:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22](Cl)=[O:23])([CH3:18])[CH3:17]>O1CCOCC1.N1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:11]([NH:14][C:22](=[O:23])[C:21]2[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=2[O:19][CH:16]([CH3:17])[CH3:18])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1

Participants

5

Reactant 2

HCID 11095854Dimethyl 4-aminoisophthalateHCID 159219142-(Propan-2-yloxy)benzoyl chloride

Product 1

HCID 20290755Dimethyl-4-(2'-isopropoxybenzoylamino)-isophthalateYield 69.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent

Procedure

Dimethyl-4-amino-isophthalate (10 g) in 10 ml of dioxane and 20 ml of anhydrous pyridine are treated with 20 g of 2-isopropoxy-benzoyl chloride at room temperature, overnight. After dilution with water, the precipitate is collected, dissolved in ethyl acetate, and washed with 5% NaHCO3 and then with water. After evaporation to dryness under vacuum, the material is crystallized from isopropyl ether, yielding dimethyl-4-(2'-isopropoxybenzoylamino)-isophthalate (12.3 g; m.p. 107°-110° C.), which is dissolved in 80 ml of dioxane and treated with 80 ml of 1 N NaOH at room temperature for one night. After acidification with dilute HCl, the precipitate is collected under vacuum and washed with water until neutral. The yield is 10.9 g of 4-(2'-isopropoxybenzoylamino)-isophthalic acid, which are treated with 60 ml of acetic anhydride at 90°-100° C. for 15'. After cooling, dilute with 60 ml of isopropyl ether and filter. The yield is 9 g of 6-carboxy-2-(2'-isopropoxyphenyl)-4H-3,1-benzoxazin-4-one (m.p. 246°-250° C.), which are reacted at room temperature first with 90 ml of 32% ammonium hydroxide and then with 45 ml of 2 N NaOH for 120'. After acidification with 4 N HCl, the precipitate is filtered off and crystallized from ethanol-chloroform to give 6-carboxy-2-(2'-isopropoxyphenyl)-3,4-dihydro-4-oxo-quinazoline (6.6 g; m.p. 316°-318° C.).

Workup

  1. customAfter dilution with water, the precipitate is collected
  2. dissolutiondissolved in ethyl acetate
  3. washwashed with 5% NaHCO3
  4. customAfter evaporation to dryness under vacuum
  5. customthe material is crystallized from isopropyl ether

Sources & evidence

ORD record
ord-dceaa41a124c43d894f942efcef78ccc
Source dataset
uspto-grants-1981_02
Patent number
US04251531

Reaction notes

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