Ethylene Glycol → 1,4-Dioxa-9-azadispiro[4.2.4.2]tetradecan-10-one

HRID 1483218Notes

Reaction equation

HRID 1483218 reaction equation
[NH:1]1[C:5]2([CH2:10][CH2:9][C:8](=[O:11])[CH2:7][CH2:6]2)[CH2:4][CH2:3][C:2]1=[O:12].[CH2:13](O)[CH2:14][OH:15]>C1(C)C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>[O:15]1[C:8]2([CH2:9][CH2:10][C:5]3([CH2:4][CH2:3][C:2](=[O:12])[NH:1]3)[CH2:6][CH2:7]2)[O:11][CH2:13][CH2:14]1

Participants

5

Reactant 2

HCID 174Ethylene GlycolHCID 114125941-Azaspiro(4.5)-decane-2,8-dione

Product 1

HCID 111834371,4-Dioxa-9-azadispiro[4.2.4.2]tetradecan-10-oneYield 95.1%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

A stirred mixture of 1-azaspiro[4.5]decane-2,8-dione (P1, 2.00 g, 12.0 mmol), ethylene glycol (2.96 g, 47.7 mmol), and 4-methylbenzenesulfonic acid (100 mg, 0.735 mmol) in toluene (100 mL) was refluxed for 20 h with Dean-Stark apparatus to remove water. After this time, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was mixed with saturated aqueous sodium bicarbonate (100 mL) and the resulting aqueous mixture was extracted with 5% methanol/ethyl acetate (4×150 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford compound P2 as an off-white solid (2.41 g, 95%): 1H NMR (300 MHz, DMSO-d6) δ 5.82 (bs, 1H), 3.95 (s, 4H), 2.41 (t, J=8.0 Hz, 2H), 1.99 (t, J=8.0 Hz, 2H), 1.80-1.65 (m, 8H). MS (M+H) 212.

Workup

  1. temperaturewas refluxed for 20 h with Dean-Stark apparatus
  2. customto remove water
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was mixed with saturated aqueous sodium bicarbonate (100 mL)
  5. extractionthe resulting aqueous mixture was extracted with 5% methanol/ethyl acetate (4×150 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0284f867e9874b56890f4ad0522708da
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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