Triethylamine → HCID 20576924, compound

HRID 1292885Notes

Reaction equation

HRID 1292885 reaction equation
[CH:1]1[CH:9]=[CH:8][C:7]2[CH2:10][CH2:11][N:5]3[C:6]=2[C:2]=1[C@H:3]1[CH2:15][NH:14][CH2:13][CH2:12][C@H:4]13.Cl[CH2:17][CH2:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)=[O:21].C(N(CC)CC)C.O1CCOCC1>C1(C)C=CC=CC=1>[CH:1]1[CH:9]=[CH:8][C:7]2[CH2:10][CH2:11][N:5]3[C:6]=2[C:2]=1[C@H:3]1[CH2:15][N:14]([CH2:17][CH2:18][CH2:19][C:20]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)=[O:21])[CH2:13][CH2:12][C@H:4]13

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 197503-(4-Fluorobenzoyl)propyl chlorideHCID 312751,4-DioxaneHCID 20576996HCID 20576996, compound

Product 1

HCID 20576924HCID 20576924, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of (±)-cis-4,5,6a,7,8,9,10,10a-octahydropyrido[4.3-b]pyrrolo[3,2,1-hi]indole (2.8 g, 14 mmol), 4-chloro-4′-fluorobutyrophenone (4.21 g, 21 mmol), triethylamine (3 mL), KI (3.48 g, 21 mmol), dioxane (25 mL), and toluene (25 mL) was stirred and refluxed for 15 h under an atmosphere of nitrogen and then evaporated under reduced pressure to remove the volatiles. The residue was triturated with a small volume of dichloromethane and decanted from the insoluble material. The process was repeated two more times and the combined dichloromethane solution was added to 0.5N solution of hydrogen chloride in ether (200 mL). The salt that separated was filtered off, washed with ether, dissolved immediately in a minimum quantity of water and the solution extracted with ether. The ether extract was discarded and aqueous layer basified with 10% aqueous sodium hydroxide. The resulting mixture was extracted with dichloro-methane (2×) and the extract dried over magnesium sulfate and stripped of the solvent under reduced pressure to yield the title compound (3.3 g, 65%) as a highly viscous light brown liquid. 1H NMR (CDCl3, 300 MHz) δ 1.70-1.80 (m, 2H), 1.80-2.02 (m, 2H), 2.19 (t, J=10.9 Hz, 1H), 2.30-2.52 (m, 3H), 2.62-2.72 (m, 1H), 2.72-2.85 (m, 1H), 2.99 (t, J=7.0 Hz, 2H), 3.02-3.20 (m, 2H), 3.25-3.42 (m, 2H), 3.59-3.65 (m, 1H), 6.85 (s, 1H), 6.90 (s, 1H0, 7.01 (t, J=7.0 Hz, 2H), 7.98-8.03 (m, 2H) ppm. MS (CI): 365 (M+H+).

Workup

  1. temperaturerefluxed for 15 h under an atmosphere of nitrogen
  2. customevaporated under reduced pressure
  3. customto remove the volatiles
  4. customThe residue was triturated with a small volume of dichloromethane
  5. customdecanted from the insoluble material
  6. additionthe combined dichloromethane solution was added to 0.5N solution of hydrogen chloride in ether (200 mL)
  7. customThe salt that separated
  8. filtrationwas filtered off
  9. washwashed with ether
  10. dissolutiondissolved immediately in a minimum quantity of water
  11. extractionthe solution extracted with ether
  12. extractionThe ether extract
  13. extractionThe resulting mixture was extracted with dichloro-methane (2×)
  14. dry with materialthe extract dried over magnesium sulfate

Sources & evidence

ORD record
ord-6df0dce88eb9459aaed54ae269e4af61
Source dataset
uspto-grants-2007_07
Patent number
US07238690B2

Reaction notes

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