Chlorotrimethylsilane → HCID 18348713, compound

HRID 2268026Notes

Reaction equation

HRID 2268026 reaction equation
[H-].[Na+].[C:3]1([CH:9]2[NH:14][C:13](=[O:15])[CH2:12][CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:16][Si](C)(C)C.C1C([N+]([O-])=O)=CC=C([Cl-][C:31]([O-])=[O:32])C=1.[O:34]=[C:35]1[N:39]([CH:40]2[CH2:45][CH2:44][N:43]([CH2:46][CH2:47][CH2:48][CH2:49][NH2:50])[CH2:42][CH2:41]2)[C:38]2[CH:51]=[CH:52][CH:53]=[CH:54][C:37]=2[NH:36]1.C(N(CC)CC)C>O1CCCC1.ClCCl>[ClH:16].[O:34]=[C:35]1[N:39]([CH:40]2[CH2:45][CH2:44][N:43]([CH2:46][CH2:47][CH2:48][CH2:49][NH:50][C:31]([N:14]3[CH:9]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:10][CH2:11][CH2:12][C:13]3=[O:15])=[O:32])[CH2:42][CH2:41]2)[C:38]2[CH:51]=[CH:52][CH:53]=[CH:54][C:37]=2[NH:36]1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 6002256-phenylpiperidin-2-oneHCID 18187426HCID 18187426, compound

Product 1

HCID 18348713HCID 18348713, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

Sodium hydride in mineral oil (60mg of a 60% suspension, 1.50 mmol) was suspended in 3 mL of tetrahydrofuran. To this suspension was added a solution of 6-phenylpiperidin-2-one (134 mg, 0.765 mmol) in tetrahydrofuran (2 mL). The resulting solution was stirred at ambient temperature for 30 minutes, then transferred via syringe to a solution of chorotrimethylsilane (500 mL, 3.94 mmol) in tetrahydrofuran (3 mL) which had already been chilled to −78° C. The reaction mixture was stirred at −78° C. for 2 hours, and then evaporated to dryness. The resulting residue was dissolved in 2 mL of tetrahydrofuran and added to a 3 mL solution of 4-nitrophenylchloroformate (154 mg, 0.764 mmol) in tetrahydrofuran which had already been chilled to 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and then at ambient temperature for 30 minutes. The mixture was evaporated to dryness, and half of the resulting residue (160 mg, 0.470 mmol) was dissolved in 5 mL of dichloromethane. To this solution was added 4-(2-keto-1-benzimidazolinyl)-piperidine butylamine (139 mg, 0.482 mmol) and triethylamine (139 mL, 0.997 mmol). The yellow reaction mixture was stirred at ambient temperature for 18 hours, and then evaporated to dryness. The resulting residue was purified by “flash” chromatography (98:2 dichloromethane:methanol). The product fractions were evaporated to an oil which was treated with HCl-saturated ethyl acetate, evaporated to dryness, and reconcentrated from diethyl ether twice to give the title compound as a solid.

Workup

  1. temperaturehad already been chilled to −78° C
  2. stirringThe reaction mixture was stirred at −78° C. for 2 hours
  3. customevaporated to dryness
  4. dissolutionThe resulting residue was dissolved in 2 mL of tetrahydrofuran
  5. temperaturehad already been chilled to 0° C
  6. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  7. waitat ambient temperature for 30 minutes
  8. stirringThe yellow reaction mixture was stirred at ambient temperature for 18 hours
  9. customevaporated to dryness
  10. customThe resulting residue was purified by “flash” chromatography (98:2 dichloromethane:methanol)
  11. customThe product fractions were evaporated to an oil which
  12. additionwas treated with HCl-saturated ethyl acetate
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-02632cc26cef4b35b582e4ca6897586d
Source dataset
uspto-grants-2001_12
Patent number
US06326372B1

Reaction notes

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