Potassium Hydroxide → 3-Acetylamino-6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]indole

HRID 379881Notes

Reaction equation

HRID 379881 reaction equation
[C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15]([C:17]1[CH:22]=[C:21]([CH2:23][O:24][Si](C(C)(C)C)(C)C)[CH:20]=[CH:19][N:18]=1)=[O:16])(=[O:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].[OH-].[K+]>C1COCC1.O>[C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15]([C:17]1[CH:22]=[C:21]([CH2:23][OH:24])[CH:20]=[CH:19][N:18]=1)=[O:16])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2724141Tetrabutylammonium FluorideHCID 183678133-Acetylamino-6-chloro-2-[4-[(tert-butyldimethylsilyloxy)methyl]pyridine-2-carbonyl]indole

Product 1

HCID 183678663-Acetylamino-6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]indoleYield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-acetylamino-6-chloro-2-[4-[(tert-butyldimethylsilyloxy)methyl]pyridine-2-carbonyl]indole (step 6, 240 mg, 0.454 mmol) in THF (10 ml) was added 1M TBAF in THF (0.7 ml, 0.681 mmol) at 0° C. After stirring for 30 min, potassium hydroxide (90 mg, 1.36 mmol) in water (2 ml) was added at 0° C. The mixture was stirred for an additional 1 h at room temperature and concentrated. The residue was diluted with ethyl acetate (100 ml), and then washed with water (30 ml×2) and dried (MgSO4). Removal of solvent gave a crystalline residue, which was recrystallized from dichloromethane to afford 52 mg (33%) of the title compound. m.p.: 216-218° C. (recrystallized from dichloromethane)

Workup

  1. stirringThe mixture was stirred for an additional 1 h at room temperature
  2. concentrationconcentrated
  3. additionThe residue was diluted with ethyl acetate (100 ml)
  4. washwashed with water (30 ml×2)
  5. dry with materialdried (MgSO4)
  6. customRemoval of solvent
  7. customgave a crystalline residue, which
  8. customwas recrystallized from dichloromethane

Sources & evidence

ORD record
ord-c78a3cb2ec1d4495b8d674f6c2c439da
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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