Diethyl Ether → HCID 22163841, compound

HRID 1087780Notes

Reaction equation

HRID 1087780 reaction equation
[H-].[Na+].O[CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]1[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[N:17][C:18]([O:24][CH3:25])=[CH:19][CH:20]=2)[N:15]=1.[CH3:26][C:27]([CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28].C(OCC)C>CN(C)C=O>[CH:29]1([C:27](=[O:28])[CH2:26][CH:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6](=[O:13])[N:5]2[C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[N:17][C:18]([O:24][CH3:25])=[CH:19][CH:20]=3)[N:15]=2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 13207Cyclohexyl methyl ketoneHCID 24758Sodium hydrideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 22163841HCID 22163841, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

An oily suspension (50% by weight; 3.1 g) of sodium hydride is added at a temperature in the region of -5° C. to a solution, maintained under a nitrogen atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (10 g) in anhydrous dimethylformamide (180 cc), and the suspension obtained is stirred for 30 minutes at a temperature in the region of 0° C. A solution of cyclohexyl methyl ketone (8.2 g) in anhydrous dimethylformamide (20 cc) is then added and stirring is continued for 6 hours at a temperature in the region of 0° C. and then for 16 hours at a temperature in the region of 20° C. The reaction mixture is then poured into distilled water (800 cc). The solid obtained is separated by filtration, washed with water, dried in the air, and then recrystallized in acetonitrile and finally purified by chromatography under pressure (50 kPa) on silica gel (0.04-0.063 mm; 140 g) contained in a column 2.8 cm in diameter. Elution is performed with methylene chloride, collecting 20-cc fractions. Fractions 25 to 62 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The solid obtained is taken up with ethyl ether (100 cc) and separated by filtration. 3-(2-Cyclohexyl-2- oxoethyl)-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (4.8 g), m.p. 140° C., is obtained.

Workup

  1. customthe suspension obtained
  2. stirringstirring
  3. waitis continued for 6 hours at a temperature in the region of 0° C.
  4. waitfor 16 hours at a temperature in the region of 20° C
  5. additionThe reaction mixture is then poured
  6. distillationinto distilled water (800 cc)
  7. customThe solid obtained
  8. customis separated by filtration
  9. washwashed with water
  10. customdried in the air
  11. customrecrystallized in acetonitrile
  12. customfinally purified by chromatography under pressure (50 kPa) on silica gel (0.04-0.063 mm; 140 g)
  13. washElution
  14. customcollecting 20-cc fractions
  15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  16. customThe solid obtained
  17. customseparated by filtration

Sources & evidence

ORD record
ord-e1b85d36aa324ccca6230b2a3f109a21
Source dataset
uspto-grants-1990_10
Patent number
US04960779

Reaction notes

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