Triethylamine → HCID 18348737, compound

HRID 2268023Notes

Reaction equation

HRID 2268023 reaction equation
[C:1]1([CH:7]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C1C([N+]([O-])=O)=CC=C([Cl-:25][C:26]([O-])=[O:27])C=1.[NH2:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)[CH2:35][CH2:34]1.C(N(CC)CC)C>O1CCCC1.ClCCl>[ClH:25].[F:45][C:42]1[CH:41]=[CH:40][C:39]([CH:36]2[CH2:35][CH2:34][N:33]([CH2:32][CH2:31][CH2:30][NH:29][C:26]([N:12]3[CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:8][CH2:9][CH2:10][C:11]3=[O:13])=[O:27])[CH2:38][CH2:37]2)=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 6002256-phenylpiperidin-2-oneHCID 101985993-(4-(4-Fluorophenyl)piperidin-1-yl)propan-1-amine

Product 1

HCID 18348737HCID 18348737, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution 6-phenylpiperidin-2-one (132 mg, 0.753 mmol) in tetrahydrofuran (3 mL) was added to a suspension of 95% sodium hydride (40 mg, 1.67 mmol) in tetrahydrofuran (3 mL). The mixture was stirred at ambient temperature for 30 minutes. The resulting solution was transferred via syringe to a solution of 4-nitrophenylchloroformate (152 mg, 0.754 mmol) in tetrahydrofuran (3 mL) which had previously been chilled to −78° C. The mixture was stirred at −78° C. for 2 hours, then evaporated to dryness. The residue was dissolved in 6 mL of dichloromethane and treated with a solution of 1-(3-aminopropyl)-4-(4-fluorophenyl)piperidine (220 mg, 0.931 mmol) in dichloromethane (4 mL) and triethylamine (209 mL, 1.50 mmol). The yellow reaction mixture was stirred at ambient temperature for 18 hours, and then evaporated to dryness. The resulting solid was purified by “flash” chromatography (98:2 dichloromethane : methanol), and the product fractions were evaporated to dryness. The resulting oil was dissolved in dichloromethane and washed six times with saturated sodium bicarbonate and once with brine. The organic phase was then dried over sodium sulfate, filtered, and the filtrate was evaporated to an oil. This residue 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 previously been chilled to −78° C
  2. stirringThe mixture was stirred at −78° C. for 2 hours
  3. customevaporated to dryness
  4. dissolutionThe residue was dissolved in 6 mL of dichloromethane
  5. stirringThe yellow reaction mixture was stirred at ambient temperature for 18 hours
  6. customevaporated to dryness
  7. customThe resulting solid was purified by “flash” chromatography (98:2 dichloromethane : methanol)
  8. customthe product fractions were evaporated to dryness
  9. dissolutionThe resulting oil was dissolved in dichloromethane
  10. washwashed six times with saturated sodium bicarbonate
  11. dry with materialThe organic phase was then dried over sodium sulfate
  12. filtrationfiltered
  13. customthe filtrate was evaporated to an oil
  14. additionThis residue was treated with HCl-saturated ethyl acetate
  15. customevaporated to dryness

Sources & evidence

ORD record
ord-053712d0e9aa422d91e67b677c7e49d9
Source dataset
uspto-grants-2001_12
Patent number
US06326372B1

Reaction notes

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