Water → HCID 21182839, compound

HRID 1387034Notes

Reaction equation

HRID 1387034 reaction equation
[OH-].[K+].[OH:3][C:4]1[C:9]2[S:10][C:11]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)=[C:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[O:14])[C:8]=2[CH:7]=[CH:6][CH:5]=1.[CH3:36]I.O>CS(C)=O>[CH3:36][O:3][C:4]1[C:9]2[S:10][C:11]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:32][CH2:33][CH2:34][CH2:35]4)=[CH:24][CH:23]=3)=[C:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[O:14])[C:8]=2[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide3×HCID 14797Potassium HydroxideHCID 21182832HCID 21182832, compound

Product 1

HCID 21182839HCID 21182839, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a suspension of powdered KOH (177 mg, 3.15 mmol) in 1.6 mL of dry DMSO was added 4-fluorophenyl 7-hydroxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (350370) (Example 75, Part G) (364 mg, 0.788 mmol) at room temperature. The reaction mixture turned orange in color. To the alkoxide was added slowly methyl iodide (49 μL, 0.79 mmol) over a period of 15 min. The reaction mixture was then stirred for 1.5 h. Another portion of MeI (20 μL, 0.32 mmol) was added, stirred for 1.5 h., followed by another addition of 20 μL (0.32 mmol) of MeI and stirring for an additional 30 min at room temperature. The reaction mixture was then poured into 20 mL of H2O. This mixture was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with H2O (5×10 mL), dried over MgSO4, and concentrated under reduced pressure. The residue was then purified by flash chromatography (silica gel, 4%[10% NH4OH in MeOH]/CH2Cl2) to afford 108 mg (0.226 mmol, 29%) of a white foam.

Workup

  1. stirringstirred for 1.5 h.
  2. stirringstirring for an additional 30 min at room temperature
  3. extractionThis mixture was extracted with CH2Cl2 (3×20 mL)
  4. washThe combined organic layers were washed with H2O (5×10 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by flash chromatography (silica gel, 4%[10% NH4OH in MeOH]/CH2Cl2)

Sources & evidence

ORD record
ord-a863a037dfcb4eb2a0dc94b7aa31179b
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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