Water → HCID 19898887, compound

HRID 1196611Notes

Reaction equation

HRID 1196611 reaction equation
[OH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[N:3]1[CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([F:30])[CH:28]=3)[NH:23][CH:22]=2)[CH2:16][CH2:15]1.O.C(=O)(O)[O-].[Na+]>C(O)(=O)C.[Zn]>[F:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[C:21]2[CH2:20][CH:17]1[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][N:3]2[CH2:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])[CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 19898892HCID 19898892, compound

Product 1

HCID 19898887HCID 19898887, compoundYield 16.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
20 °C

Procedure

Powdered zinc (2.97 g) is added at a temperature in the region of 20° C. to a stirred solution of (RS)-3-hydroxy-2-{2-[4-((5-fluoro-3-indolyl)methyl)piperidino]ethyl}isoindolinone (3.4 g) in acetic acid (21 cc). The mixture is heated to boiling for 9 hours and then cooled to a temperature in the vicinity of 20° C. After the addition of distilled water (30 cc), the solution is alkalinized to pH 7-8 with sodium bicarbonate. The organic phase is extracted with dichloromethane (4×30 cc), washed with distilled water (30 cc), dried over anhydrous magnesium sulphate, treated with vegetable charcoal, filtered and concentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is purified by flash chromatography on a silica column under a stream of argon at moderate pressure (0.5-1.5 bar) with ethyl acetate and then a mixture of ethyl acetate and methanol (98:2 by volume) as eluents. After recrystallization in ethyl acetate (40 cc), 2-{2-[4-((5-fluoro-3-indolyl)methyl)piperidino]ethyl}isoindolinone (0.54 g), m.p. 175° C., is obtained.

Workup

  1. temperatureThe mixture is heated
  2. extractionThe organic phase is extracted with dichloromethane (4×30 cc)
  3. washwashed with distilled water (30 cc)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. additiontreated with vegetable charcoal
  6. filtrationfiltered
  7. concentrationconcentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
  8. customThe residue obtained
  9. customis purified by flash chromatography on a silica column under a stream of argon at moderate pressure (0.5-1.5 bar) with ethyl acetate
  10. additiona mixture of ethyl acetate and methanol (98:2 by volume) as eluents
  11. customAfter recrystallization in ethyl acetate (40 cc)

Sources & evidence

ORD record
ord-cf8cf23f74e04f9881a67bc0d8d83b46
Source dataset
uspto-grants-1992_05
Patent number
US05114949

Reaction notes

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