Triethylamine → 1,3-Dihydro-1-piperidin-4-yl-2H-benzimidazole-2-thione

HRID 1295771Notes

Reaction equation

HRID 1295771 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][CH:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[NH2:19])[CH2:8][CH2:7]1)=O)C.C(N(CC)CC)C.[C:27](Cl)(Cl)=[S:28]>C(Cl)Cl>[NH:6]1[CH2:7][CH2:8][CH:9]([N:12]2[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[NH:19][C:27]2=[S:28])[CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10040ThiophosgeneHCID 13046883Ethyl 4-(2-aminoanilino)piperidine-1-carboxylate

Product 1

HCID 30344491,3-Dihydro-1-piperidin-4-yl-2H-benzimidazole-2-thioneYield 29.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(2-amino-phenylamino)-piperidine-1-carboxylic acid ethyl ester (0.76 g, 2.9 mmol) and triethylamine (0.81 ml, 5.8 mmol) in methylene chloride (10 mL) at 0° C. was added a solution of thiophosgene (0.22 mL, 2.9 mmol) in methylene chloride (10 mL) at room temperature. The reaction mixture was stirred for 2 h then quenched with 1N sodium hydroxide. The organic phase was separated and dried over sodium sulfate, filtered and concentrated. The crude product (i.e.; 4-(2-thioxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester) was treated with 10% sodium hydroxide (10 mL) and refluxed for 4 h. The reaction was allowed to cool to room temperature and the aqueous layer was washed with ethyl ether (50 mL), acidified to pH<2 with 6N hydrochloric acid, washed with ethyl ether (50 ml) and filtered (to remove a small amount of precipitated solid). The aqueous layer was adjusted to pH 10 by slowly adding sodium carbonate and then cooled to 0° C. The solid that formed was collected by filtration to give 1-piperidin-4-yl-1,3-dihydro-benzoimidazole-2-thione (0.2 g).

Workup

  1. customthen quenched with 1N sodium hydroxide
  2. customThe organic phase was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe crude product (i.e.; 4-(2-thioxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester) was treated with 10% sodium hydroxide (10 mL)
  7. temperaturerefluxed for 4 h
  8. washthe aqueous layer was washed with ethyl ether (50 mL)
  9. washwashed with ethyl ether (50 ml)
  10. filtrationfiltered (
  11. customto remove a small amount of precipitated solid)
  12. temperaturecooled to 0° C
  13. customThe solid that formed
  14. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-2bb518583dfc4c7ab354cd5137616fff
Source dataset
uspto-grants-2007_07
Patent number
US07244744B2

Reaction notes

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