Hydrochloric Acid → 1-[2-(Piperidin-1-yl)ethyl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 1059649Notes

Reaction equation

HRID 1059649 reaction equation
[C:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:13])([CH3:3])=C.[H-].[Na+].Cl.ClCC[N:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.Cl>CN(C=O)C.O>[N:20]1([CH2:3][CH2:1][N:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[NH:6][C:5]2=[O:13])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydride2×HCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 1002781,3-Dihydro-1-(1-methylvinyl)-2H-benzimidazol-2-one

Product 1

HCID 140536861-[2-(Piperidin-1-yl)ethyl]-1,3-dihydro-2H-benzimidazol-2-oneYield 46.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
45 °C

Procedure

A solution of 1-isopropenyl-1,3-dihydro-2H-benzimidazol-2-one (35 g, 0.2 moles) in DMF (250 ml) was added dropwise to a suspension of 80% sodium hydride (6 g, 0.2 moles) in DMF (50 ml). The reaction mixture was first heated at 45° C. for 30 minutes, allowed to cool at room temperature, and an additional amount of 80% sodium hydride (7.2 g, 0.24 moles) was added. Then 1-(2-chloroethyl)piperidine hydrochloride (44.16 g, 0.24 moles) was added portionwise and the reaction mixture was heated at 80° C.-90° C. for 3 hours. The mixture was then cooled at room temperature, adjusted to pH 3 with 37% aqueous HCl, and heated to 80° C. for additional 2 hours. The reaction mixture was poured into water and washed with ethyl acetate. The aqueous phase was adjusted to pH 8-9 with a saturated sodium carbonate solution and extracted into ethyl acetate. The organic layer was taken to dryness to give an ivory solid which after crystallization from isopropyl ether afforded 22.9 g of the title compound. M.p. 123° C.-125° C.

Workup

  1. temperatureto cool at room temperature
  2. temperaturethe reaction mixture was heated at 80° C.-90° C. for 3 hours
  3. temperatureThe mixture was then cooled at room temperature
  4. temperatureheated to 80° C. for additional 2 hours
  5. washwashed with ethyl acetate
  6. extractionextracted into ethyl acetate
  7. customto give an ivory solid which
  8. customafter crystallization from isopropyl ether

Sources & evidence

ORD record
ord-4be058c9bc984dc6b751fb4cad765378
Source dataset
uspto-grants-2003_02
Patent number
US06521623B1

Reaction notes

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