1,1'-Carbonyldiimidazole → Thalidomide

HRID 1531850Notes

Reaction equation

HRID 1531850 reaction equation
[CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([C@H:12]([C:18]([OH:20])=O)[CH2:13][CH2:14][C:15]([NH2:17])=[O:16])[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C1C=CN=CC=1.O1CCCC1>[CH:2]1[CH:1]=[CH:6][C:5]2[C:7](=[O:8])[N:9]([CH:12]3[C:18](=[O:20])[NH:17][C:15](=[O:16])[CH2:14][CH2:13]3)[C:10](=[O:11])[C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 259136N-Phthaloyl-L-glutamine

Product 1

HCID 5426ThalidomideYield 90%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A stirred mixture of N-phthaloyl-L-glutamine (48.0 g, 174 mmoL), carbonyldimidazole (30.43 g, 188 mmoL), and 4-dimethylaminopyridine (0.105 g, 0.861 mmoL) in anhydrous tetrahydrofuran (300 mL) is heated to reflux for 16 hours. The reaction slurry is filtered and the solid washed with methylene chloride (200 mL). The solid is air-dried and then dried in vacuo (60° C., <1 mm) to afford 40.40 g (90%) of thalidomide as a white powder. 1H NMR (DMSO-d6) δ11.16 (s, 1H, NH), 8.05-7.80 (br s, 4H, Ar), 5.18 (dd, 1H, J=12, 5 Hz, CHCO), 3.05-2.85 (m, 1H, CH2CO), 2,70-2.45 (m, 2H, CH2CH2); 2.15-2.00 (M, 1H, CH2). 13C NMR (DMSO-d6) δ172.8, 169.8, 167.1, 134.9, 131.2, 123.4, 49.0, 30.9, 22.0.

Workup

  1. temperatureis heated
  2. temperatureto reflux for 16 hours
  3. filtrationThe reaction slurry is filtered
  4. washthe solid washed with methylene chloride (200 mL)
  5. customThe solid is air-dried
  6. customdried in vacuo (60° C., <1 mm)

Sources & evidence

ORD record
ord-d0c17029e3ba419f84de828542487049
Source dataset
uspto-grants-2001_03
Patent number
US06200987B1

Reaction notes

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