Ethylene Glycol → 8-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]propyl}-6-(trifluoromethyl)-1,2,7,8,9,10-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole

HRID 50982Notes

Reaction equation

HRID 50982 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:32])[CH2:9][CH2:10][CH2:11][N:12]2[CH2:31][CH2:30][C:15]3[N:16]4CCO[C:18]5[CH:19]=[CH:20][C:21]([C:23]([F:26])([F:25])[F:24])=[C:22]([C:17]4=5)[C:14]=3[CH2:13]2)=[CH:4][CH:3]=1.[CH2:33]([OH:36])[CH2:34]O.CC1C=[CH:40][C:41]([S:44](O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:9][CH2:10][CH2:11][N:12]3[CH2:31][CH2:30][C:15]4[N:16]5[CH2:40][CH2:41][S:44][C:18]6[CH:19]=[CH:20][C:21]([C:23]([F:26])([F:24])[F:25])=[C:22]([C:17]5=6)[C:14]=4[CH2:13]3)[O:36][CH2:33][CH2:34][O:32]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 22735702HCID 22735702, compound

Product 1

HCID 227359508-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]propyl}-6-(trifluoromethyl)-1,2,7,8,9,10-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-(4-Fluorophenyl)-4-(6-(trifluoromethyl)-1,2,9,10-tetrahydro[1,4]oxazino[2,3,4-hi]pyrido[4,3-b]indol-8(7H)-yl)-1-butanone (70 mg, 0.15 mmol) and ethylene glycol (10.4 mg, 0.17 mmol) were mixed together in anhydrous toluene (5 mL) in a round bottom flask equipped with a Dean-Stark apparatus and 3 Å molecular sieves. A few crystals of p-TsOH were added and reaction was heated to reflux for 5 hours. The reaction mixture was concentrated under reduced pressure and then extracted with dichloromethane (2×25 mL), washed with saturated sodium carbonate (1×15 mL) and brine (1×15 mL), dried (sodium sulfate) and concentrated. Product was purified by preperative thin layer chromatography on silica gel, and eluted with 10% MeOH in dichloromethane to give the title compound. 1H NMR (CDCl3, 300 MHz): δ8.00-7.95 (m, 2H), 7.10-6.92 (m, 4H), 4.30-4.26 (m, 2H), 4.03-4.00 (m, 1H), 3.79-3.71 (m, 3H), 3.28-3.23 (m, 2H), 2.92-2.82 (m, 5H), 2.73 (t, 2H, J=7.1 Hz), 2.60 (t, 1H, J=7.5 Hz), 2.10-2.05 (m, 2H) ppm.

Workup

  1. customequipped with a Dean-Stark apparatus and 3 Å molecular sieves
  2. customreaction
  3. temperaturewas heated
  4. temperatureto reflux for 5 hours
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. extractionextracted with dichloromethane (2×25 mL)
  7. washwashed with saturated sodium carbonate (1×15 mL) and brine (1×15 mL)
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated
  10. customProduct was purified by preperative thin layer chromatography on silica gel
  11. washeluted with 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-aee6f009c01244b58cf0033317a751a4
Source dataset
uspto-grants-2004_03
Patent number
US06713471B1

Reaction notes

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