Triethylamine → HCID 18348704, compound

HRID 2268027Notes

Reaction equation

HRID 2268027 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.C1C([N+]([O-])=O)=CC=C([Cl-:25][C:26]([O-])=[O:27])C=1.[C:29]([C:31]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][CH2:39][NH2:40])[CH2:33][CH2:32]1)#[N:30].C(N(CC)CC)C>O1CCCC1.ClCCl>[ClH:25].[C:29]([C:31]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:32][CH2:33][N:34]([CH2:37][CH2:38][CH2:39][NH:40][C:26]([N:14]2[CH:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:10][CH2:11][CH2:12][C:13]2=[O:15])=[O:27])[CH2:35][CH2:36]1)#[N:30]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 6002256-phenylpiperidin-2-oneHCID 98377104-Cyano-4-phenylpiperidine propylamine

Product 1

HCID 18348704HCID 18348704, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride in mineral oil (60%, 65 mg, 1.63 mmol) was suspended in 3 mL of tetrahydrofuran. To this suspension was added 3 mL of a solution of 6-phenylpiperidin-2-one (235 mg, 1.34 mmol) and the mixture was stirred at ambient temperature for 30 minutes. The resulting solution was transferred via syringe to solution of 4-nitrophenylchloroformate (269 mg, 1.33 mmol) in tetrahydrofuran (4 mL) which had already been chilled to −78° C. The reaction mixture was stirred at −78° C. for 2 hours and then at ambient temperature for 30 minutes. The reaction mixture was then evaporated to dryness. One third of the resulting residue (150 mg, 0.441 mmol) was dissolved in 5 mL of dichloromethane. 4-cyano-4-phenylpiperidine propylamine (113 mg, 0.464 mmol) and triethylamine (139 mL, 0.997 mmol) were added to this solution, and the resulting yellow mixture was stirred at ambient temperature for 18 hours, and then evaporated to dryness. The resulting residue was purified by “flash” chromatography (97:3:0.3 dichloromethane:methanol:ammonium hydroxide). The product fractions were evaporated to give a yellow oil. The residue was purified by “flash” chromatography (1:1 ethyl acetate:hexanes). The product fractions were evaporated to dryness. The residue was then 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. waitat ambient temperature for 30 minutes
  4. customThe reaction mixture was then evaporated to dryness
  5. stirringthe resulting yellow mixture was stirred at ambient temperature for 18 hours
  6. customevaporated to dryness
  7. customThe resulting residue was purified by “flash” chromatography (97:3:0.3 dichloromethane:methanol:ammonium hydroxide)
  8. customThe product fractions were evaporated
  9. customto give a yellow oil
  10. customThe residue was purified by “flash” chromatography (1:1 ethyl acetate:hexanes)
  11. customThe product fractions were evaporated to dryness
  12. additionThe residue was then treated with HCl-saturated ethyl acetate
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-7ae9b8b682244276908827078d04b72f
Source dataset
uspto-grants-2001_12
Patent number
US06326372B1

Reaction notes

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