Water → Benzenesulfonic acid 3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester

HRID 1766263Notes

Reaction equation

HRID 1766263 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.[H-].[Na+].[C:20]1([S:26](Cl)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>CN(C)C=O>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][S:26]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)(=[O:28])=[O:27])[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 24383-(1-Methyl-4-piperidinyl)-1H-indol-5-olHCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydride

Product 1

HCID 10270511Benzenesulfonic acid 3-(1-methylpiperidin-4-yl)-1H-indol-5-yl esterYield 70.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole (4.75 g, 20.6 mmol) in dimethylformamide (25 mL), stirring at 0° C. under nitrogen, was added sodium hydride in one portion (0.83 g of a 60% dispersion in oil, 20.6 mmol). The green solution turned brown; after stirring for 30 minutes at 0° C. benzenesulfonyl chloride (2.63 mL, 20.6 mmol) was added in one portion, then the reaction mixture was allowed to stir until the reaction was complete. The solution was poured into water (125 mL), then extracted with ethyl acetate (4×125 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo to a residue which was further purified on silica gel. Elution with a 9:1 mixture of dichloromethane and 2 N ammonia in methanol provided 5.40 g (70%) of benzenesulfonic acid 3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester as a tan solid: mp=189-194° C.; 1H NMR (400 MHz, dmso-d6): 10.97 (br s, 1H), 7.85-7.72 (m, 3H), 7.65-7.54 (mm, 2H), 7.24 (d, 1H, J=8.8 Hz), 7.11 (d, 1H, J=2.0 Hz), 6.88 (d, 1H, J=1.2 Hz), 6.69 (dd, 1H, J=8.8, 1.6 Hz), 2.77 (br d, 2H, J=11.2 Hz), 2.52-2.40 (m, 1H), 2.16 (s, 3H), 1.91 (br t, 2H, J=11.2 Hz), 1.67 (br d, 2H, J=12.0 Hz), 1.58-1.44 (m, 2H); MS(ES+): m/e 371.0 (M+1).

Workup

  1. additionwas added in one portion
  2. extractionextracted with ethyl acetate (4×125 mL)
  3. dry with materialThe combined organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to a residue which
  6. customwas further purified on silica gel
  7. washElution
  8. additionwith a 9:1 mixture of dichloromethane and 2 N ammonia in methanol

Sources & evidence

ORD record
ord-a19e6ca82eb4495aa2f36627801d0de3
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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