1,1'-Carbonyldiimidazole → Thalidomide

HRID 1417365Notes

Reaction equation

HRID 1417365 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), carbonyldiimidazole (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. 1HNMR (DMSO-d6) δ 11.16 (s, 1 H, NH), 8.05-7.80 (br s, 4 H, Ar), 5.18 (dd, 1 H, J=12, 5 Hz, CHCO), 3.05-2.85 (m, 1 H, CH2CO), 2,70-2.45 (m, 2 H, CH2CH 2), 2.15-2.00 (M, 1 H, CH2). 13C NMR (DMSO-d6) δ 172.8, 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-e4454a1370144876b18e66cd63c347ac
Source dataset
uspto-grants-1999_03
Patent number
US05877200

Reaction notes

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