1,3-Propanediol → 5'-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

HRID 853842Notes

Reaction equation

HRID 853842 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2=[O:22])(=[O:11])=[O:10].[CH2:23](O)[CH2:24][CH2:25][OH:26]>C1C=CC=CC=1>[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]12[O:26][CH2:25][CH2:24][CH2:23][O:22]1)(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 104421,3-PropanediolHCID 9840223Mmpsi

Product 1

HCID 589325505'-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-oneYield 45%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 5-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}-1H-indole-2,3-dione (13.41 g, 41.3 mmol), 1,3 propanediol (12.1 mL, 165 mmol, 4eq) and p-tolune sulfonic acid (3.14 g, 16.5 mmol, 0.4 mole %) in benzene (800 mL) was heated to reflux under a Dean Stark Trap for 5 hours and stirred overnight at room temperature. The mixture was washed with saturated aqueous NaHCO3 (3×300 mL), water (3×300 mL) and brine (3×300 mL), dried over sodium sulfate, filtered, and concentrated to give 10.7 g of crude product that was flash chromatographed (Biotage KP silica gel, step gradient 60/40-50/50 Pet Ether/EtOAc) to give the title compound as a white solid (7.1 g, 45% yield). Anal: Calc'd for C17H22N2O6S: C, 53.39; H, 5.80; N, 7.32; Found: C, 53.08; H,5.82; N, 6.92; NMR (400 MHz, DMSO-d6): consistent. IR: consistent. MS: (ES−) m/z 381 [M−H]. m.p: 127-128° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under a Dean Stark Trap for 5 hours
  3. washThe mixture was washed with saturated aqueous NaHCO3 (3×300 mL), water (3×300 mL) and brine (3×300 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give 10.7 g of crude product that
  8. customchromatographed (Biotage KP silica gel, step gradient 60/40-50/50 Pet Ether/EtOAc)

Sources & evidence

ORD record
ord-feb3ab0d0c8543a180533c51a23c1f43
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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