Water → HCID 18980211, compound

HRID 2392581Notes

Reaction equation

HRID 2392581 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][N:26]4[C:34](=O)[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[C:27]4=O)[CH2:18][CH2:17]3)=[CH:14][S:13][C:12]=2[CH:37]=1.O.[OH-].[Na+]>O1CCCC1>[F:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([N:16]3[CH2:17][CH2:18][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][N:26]4[CH:27]=[C:28]5[C:33]([CH:32]=[CH:31][CH:30]=[CH:29]5)=[CH:34]4)[CH2:20][CH2:21]3)=[CH:14][S:13][C:12]=2[CH:37]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 18980218HCID 18980218, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 18980211HCID 18980211, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of LiAlH4 (1.50 g, 37.9 mmol) in anhydrous tetrahydrofuran (100 mL) under a nitrogen atmosphere at room temperature was added dropwise a solution of 2-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)-dione (5.95 g, 13.6 mmol) in anhydrous tetrahydrofuran (125 mL) over 20 minutes. After the addition the reaction was stirred at 50° C. for 4 hours and then cooled to room temperature. The reaction was treated sequentially with water (1.5 mL), 15% NaOH (1.5 mL), and water (4.5 mL) and stirred at room temperature for 0.5 hours. The mixture was filtered, the insolubles washed with CHCl3 (2 ×50 mL), and the filtrate concentrated in vacuo. The residue was dissolved in chloroform (200 mL), washed with water (100 mL), dried (K2CO3), and the solvent removed in vacuo. The crude product was chromatographed on silica gel with 10% methanol in dichloromethane as eluent to afford 3.50 g of a tan solid. The solid was recrystallized twice from ethyl acetate to afford 1.48 g (26%) of the title compound as amber crystals, m.p. 118°-120° C.

Workup

  1. additionAfter the addition the reaction
  2. temperaturecooled to room temperature
  3. stirringstirred at room temperature for 0.5 hours
  4. filtrationThe mixture was filtered
  5. washthe insolubles washed with CHCl3 (2 ×50 mL)
  6. concentrationthe filtrate concentrated in vacuo
  7. dissolutionThe residue was dissolved in chloroform (200 mL)
  8. washwashed with water (100 mL)
  9. dry with materialdried (K2CO3)
  10. customthe solvent removed in vacuo
  11. customThe crude product was chromatographed on silica gel with 10% methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-f750cb0cd3b94d9d946c52a2b4d1e6d6
Source dataset
uspto-grants-1998_09
Patent number
US05801176

Reaction notes

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