Water → HCID 21444381, compound

HRID 328281Notes

Reaction equation

HRID 328281 reaction equation
[BH4-].[K+].[Cl:3][C:4]1C=[C:6]2[C:11](=O)[N:10]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[N:16][C:17]([Cl:23])=[CH:18][CH:19]=4)[N:14]=3)C(=O)[C:7]2=[CH:24][CH:25]=1.[OH2:26].[O:27]1[CH2:32][CH2:31]OCC1>CO>[Cl:3][C:4]1[CH:25]=[CH:24][CH:7]=[C:6]2[C:31]=1[CH:32]([OH:27])[N:10]([C:13]1[CH:22]=[CH:21][C:20]3[C:15](=[N:16][C:17]([Cl:23])=[CH:18][CH:19]=3)[N:14]=1)[C:11]2=[O:26]

Participants

6

Reactant 4

HCID 962WaterHCID 312751,4-DioxaneHCID 4192641Potassium borohydrideHCID 214443605-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 21444381HCID 21444381, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Potassium borohydride (3 g.) is added to 4-chloro-N-(7-chloro-1,8-naphthyridin-2-yl)-phthalimide (25.2 g.) in dioxane (500 cc.) and methanol (500 cc.). The mixture is stirred for 4 hours at a temperature of about 20° C and water (500 cc.) is then added. The precipitate is filtered off and washed with water (100 cc.) and then with a mixture (200 cc.) of equal parts of methanol and dioxane. This gives a crude product (20 g.) which is chromatographed on silica (0.05 - 0.2 mm) (6 kg.) as indicated below, the eluate being collected in fractions of 5,000 cc. Elution is carried out first with methylene chloride (10,000 cc.) and then with a mixture of methylene chloride and ethyl acetate (5/5 by volume) (40,000 cc.). This eluate, after concentration, yields (4-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone (6 g.) melting at 270° C. Thereafter elution is carried out with the same mixture of methylene chloride and ethyl acetate (10,000 cc.). This eluate, after concentration, gives a mixture (1.6 g.) of the isomers 4-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone and 7-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone. Finally, elution is carried out again with the same mixture of methylene chloride and ethyl acetate (20,000 cc.). This eluate, after concentration, yields 7-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone (3.1 g.) melting at a temperature above 280° C.

Workup

  1. additionis then added
  2. filtrationThe precipitate is filtered off
  3. washwashed with water (100 cc.)
  4. customThis gives a crude product (20 g.) which
  5. customis chromatographed on silica (0.05 - 0.2 mm) (6 kg.)
  6. custombeing collected in fractions of 5,000 cc
  7. washElution
  8. additionwith a mixture of methylene chloride and ethyl acetate (5/5 by volume) (40,000 cc.)
  9. concentrationThis eluate, after concentration

Sources & evidence

ORD record
ord-ecd4b38af28343dda791158f590076a8
Source dataset
uspto-grants-1977_04
Patent number
US04016274

Reaction notes

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