Triethylamine → 1-Tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine

HRID 1354250Notes

Reaction equation

HRID 1354250 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[F:29][C:30]1[C:39]([F:40])=[CH:38][C:33]2[N:34]=[C:35]([SH:37])[NH:36][C:32]=2[CH:31]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>C1COCC1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:37][C:35]2[NH:36][C:32]3[CH:31]=[C:30]([F:29])[C:39]([F:40])=[CH:38][C:33]=3[N:34]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 31297Methanesulfonyl chlorideHCID 735736Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 106791065,6-difluoro-1H-benzimidazole-2-thiol

Product 1

HCID 117110271-Tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazineYield 68%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-tert-butoxycarbonyl-4-(2-hydroxyethyl)piperazine (7.40 g, 32.13 mmol) in THF (100 mL), while stirring in an ice-bath, triethylamine (4.36 g, 43.09 mmol), 4-dimethylaminopyridine (200 mg, 1.64 mmol), and methanesulfonyl chloride (7.40 g, 38.76 mmol) were sequentially added. The temperature of the mixture was allowed to room temperature, and the mixture was stirred for 50 minutes. The reaction mixture was filtrated, and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (200 mL), and, at room temperature, 5,6-difluoro-2-mercaptobenzimidazole (5.00 g, 26.86 mmol), potassium carbonate (8.64 g, 62.51 mmol), and 18-crown-6 (500 mg, 1.92 mmol) were sequentially added to the solution, followed by stirring for 90 minutes at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1). The product was crystallized from acetone-ether-hexane, to thereby yield 1-tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine (7.26 g, yield 68%) as colorless crystals.

Workup

  1. customwas allowed to room temperature
  2. filtrationThe reaction mixture was filtrated
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (200 mL)
  5. stirringby stirring for 90 minutes at 80° C
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1)
  8. customThe product was crystallized from acetone-ether-hexane

Sources & evidence

ORD record
ord-afd6da84661d43fa9da70f4253b5befa
Source dataset
uspto-grants-2007_05
Patent number
US07223764B2

Reaction notes

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