Thalidomide → 2-(1-(2-Hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

HRID 1525806Notes

Reaction equation

HRID 1525806 reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[CH2:6][CH2:5][C:4](=[O:19])[NH:3]1.[H-].[Na+].Cl[CH:23]([OH:25])[CH3:24]>CN(C=O)C.O>[OH:25][CH2:23][CH2:24][N:3]1[C:4](=[O:19])[CH2:5][CH2:6][CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[C:2]1=[O:1]

Participants

6

Reactant 3

HCID 5426ThalidomideHCID 24758Sodium hydrideHCID 126390351-Chloroethan-1-ol

Product 1

HCID 119652712-(1-(2-Hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(2,6-Dioxopiperidin-3-yl)isoindoline-1,3-dione (2.5 g) was dissolved in DMF (dry, 60 mL). 95% NaH (0.24 g) was added. The mixture was stirred for 30 minutes at room temperature. Then, chioroethanol (0.68 mL) was added, and the mixture was stirred over night at room temperature. The reaction mixture was diluted with 300 mL of water and extracted with ethyl acetate (3×60 mL). Organic phases were combined and washed twice with water, and once with brine, then dried over anhydrous magnesium sulfate. Rotary evaporation of solvent yielded crude product, which was purified by silica gel column chromatography (acetic ether: petroleum ether=1:1) to yield 1.1 g of pure title product. 1H NMR (CDCl3, ppm) δ 7.88-7.90 (m, 2H), 7.77-7.79 (m, 2H), 5.06 (dd, 1H, J=5.6, 12.4Hz), 4.02-4.12 (m, 2H), 3.76-3.80 (m, 2H), 2.94-3.02 (m, 1H), 2.72-2.90 (m, 2H), 2.29-2.31 (m, 1H), 2.14-2.23 (m, 1H).

Workup

  1. stirringthe mixture was stirred over night at room temperature
  2. extractionextracted with ethyl acetate (3×60 mL)
  3. washwashed twice with water
  4. dry with materialonce with brine, then dried over anhydrous magnesium sulfate
  5. customRotary evaporation of solvent
  6. customyielded crude product, which
  7. customwas purified by silica gel column chromatography (acetic ether: petroleum ether=1:1)

Sources & evidence

ORD record
ord-9d95e33c00f14e56848b8b7f48dbe35f
Source dataset
uspto-grants-2015_07
Patent number
US09085563B2

Reaction notes

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