p-Toluenesulfonic acid → 5'-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

HRID 853874Notes

Reaction equation

HRID 853874 reaction equation
[N:1]1([S:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13](=[O:18])[C:12]3=[O:19])(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:20](O)[CH2:21][CH2:22][OH:23].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[N:1]1([S:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13](=[O:18])[C:12]23[O:23][CH2:22][CH2:21][CH2:20][O:19]2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 104421,3-PropanediolHCID 41173815-(Pyrrolidin-1-ylsulfonyl)indoline-2,3-dione

Product 1

HCID 589325715'-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-oneYield 168.9%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A stirred mixture of 5-(pyrrolidin-1-ylsulfonyl)-1H-indole-2,3-dione (0.88 g, 3.14 mmol), 1,3-propanediol (0.92 mL, 1.26 mmol, 4 eq) and p-toluenesulfonic acid (1.19 g, 6.28 mmol, 0.2 mole % ) in benzene (100 mL) was refluxed with a Dean Stark Trap for 6 hours. The reaction was cooled to room temperature, washed with sat. aq. NaHCO3 (1×), water (2×), and brine (1×), dried over NaHCO3 (1×,), filtered and concentrated. The crude product was purified on Biotage KP silica gel eluting with 90/10 CH2Cl2/EtOAc to give the title compound as a white solid (0.72 g, 68% ). NMR (300 Mz, DMSO-d6): consistent. MS: (API-ES+) 338 [M+H] consistent.

Workup

  1. temperaturewas refluxed with a Dean Stark Trap for 6 hours
  2. washwashed with sat. aq. NaHCO3 (1×), water (2×), and brine (1×)
  3. dry with materialdried over NaHCO3 (1×,)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified on Biotage KP silica gel eluting with 90/10 CH2Cl2/EtOAc

Sources & evidence

ORD record
ord-a5197072a36449a091d8ab1d616124c9
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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