Chloroacetyl chloride → HCID 67229950, compound

HRID 448300Notes

Reaction equation

HRID 448300 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20].[Cl:29][CH2:30][C:31](Cl)=[O:32]>C1COCC1>[Cl:29][CH2:30][C:31]([NH:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20])=[O:32]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 67229950HCID 67229950, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.7 g, 6.5 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.8 g, 2.6 mmol) in THF (50 mL). After stirring for 5 minutes, chloroacetyl chloride (0.4 g, 3.6 mmol) was added slowly. The resulting brown suspension was refluxed overnight. The mixture was cooled and quenched with methanol (1 mL). The mixture was concentrated, and the solid was stirred with 0.5N HCl (30 mL). The mixture was filtered, and the solid was slurried with ethanol (15 mL) to give 2-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.7 g, 76%): 1H NMR (DMSO-d6) δ 1.99-2.04 (m, 1H), 2.35-2.65 (m, 2H), 2.85-2.94 (m, 1H), 4.19 (s, 2H, CH2), 5.10-5.18 (dd, J=5.1 and 13.3 Hz, 1H, CH), 7.50-7.66 (m, 3H), 8.80 (t, J=5.7 Hz, 1H, NH), 11.01 (s, 1H, NH).

Workup

  1. temperatureThe resulting brown suspension was refluxed overnight
  2. temperatureThe mixture was cooled
  3. customquenched with methanol (1 mL)
  4. concentrationThe mixture was concentrated
  5. stirringthe solid was stirred with 0.5N HCl (30 mL)
  6. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-8f55b4d9402c44398287fa9d69282205
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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