Ammonia → HCID 22562192, compound

HRID 982631Notes

Reaction equation

HRID 982631 reaction equation
[CH3:1][C:2]1([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[NH:18][C:17]3=O)[CH2:12][CH2:11]2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.P(Cl)(Cl)([Cl:28])=O.N>>[Cl:28][C:17]1[N:16]([CH:13]2[CH2:14][CH2:15][N:10]([C:2]3([CH3:1])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]3)[CH2:11][CH2:12]2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=1

Participants

4

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 69707236HCID 69707236, compound

Product 1

HCID 22562192HCID 22562192, compoundYield 66.3%

Procedure

A mixture of 4-(2-keto-1-benzimidazolinyl)piperidine (5.10 g, 23.5 mmol) and HCl solution in MeOH (20 ml) was stirred at room temperature for 10 minutes. After evaporation of the solvent, the residue was triturated in Et2O to give HCl salt as off-white powder. To this HCl salt was added cyclooctanone (3.33 ml, 28.2 mmol) followed by addition of aqueous solution of KCN (1.92 g, 29.5 mmol) in water (7 ml) at room temperature. After 18 hour stirring, the resulting solid was collected by filtration, washed with water, and dried in vacuo to give 6.81 g (85.7%) of nitrile derivative as white powder. To a solution of this nitrile derivative (5.12 g, 15.1 mmol) in THF (40 ml) was added a solution of methylmagnesium bromide in Et2O (3.0 M solution, 25 ml) at 0° C. Then the reaction mixture was stirred at room temperature for 18 hours. Aqueous NH4Cl solution was added to the reaction mixture and the resulting solid appeared was collected by filtration, washed with water and Et2O, and dried in vacuo at 70° C. to give 4.88 g (82.8%) of 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-1,3-dihydro-2H-1,3-benzimidazol-2-one as white powder. A mixture of 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-1,3-dihydro-2H-1,3-benzimidazol-2-one (2.316 g, 5.95 mmol) and phosphoryl chloride (15 ml, 165.5 mmol) was heated to reflux for 1.5 h. After cooling down to room temperature, the reaction mixture was poured into ice cooled 25% ammonia solution and extracted with CH2Cl2. The extracts combined were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel: 200 g, hexane/ethyl acetate: 4/1) to give 1.42 g(58.7%) of a colorless amorphous solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1.5 h
  3. additionthe reaction mixture was poured into ice
  4. extractionextracted with CH2Cl2
  5. washThe extracts combined were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (silica gel: 200 g, hexane/ethyl acetate: 4/1)

Sources & evidence

ORD record
ord-57a2324963494f43bfddd9fed6a3510c
Source dataset
uspto-grants-2005_03
Patent number
US06861425B2

Reaction notes

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