Boron trifluoride → HCID 71008754, compound

HRID 1887488Notes

Reaction equation

HRID 1887488 reaction equation
[F:1][C:2]([F:22])([F:21])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][CH:14]3[CH2:17][NH:18][CH2:19][CH:13]3[C:12]2=[O:20])=[CH:7][CH:6]=1.I[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[O:30]C.C(O[K])(C)(C)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.FB(F)F>C1(C)C=CC=CC=1.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[OH:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[N:18]1[CH2:17][CH:14]2[CH:13]([C:12](=[O:20])[N:11]([C:8]3[CH:9]=[CH:10][C:5]([O:4][CH2:3][C:2]([F:1])([F:21])[F:22])=[CH:6][CH:7]=3)[CH2:16][CH2:15]2)[CH2:19]1

Participants

10

Reactant 5

HCID 6356Boron trifluorideHCID 68257o-IodoanisoleHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 71008531HCID 71008531, compoundHCID 178418922HCID 178418922, compound

Product 1

HCID 71008754HCID 71008754, compoundYield 69%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 5-[4-(2,2,2-Trifluoro-ethoxy)-phenyl]-octahydro-pyrrolo[3,4-c]pyridin-4-one (200 mg, 0.6 mmol), 1-iodo-2-methoxybenzene (300 mg, 1.3 mmol), Pd2(dba)3 (100 mg, 0.1 mmol), tBuOK (200 mg, 1.8 mmol) and 2-(Di-tert-butylphosphino)biphenyl (200 mg, 0.7 mmol) in toluene (20 mL) was refluxed overnight under nitrogen atmosphere. The mixture was cooled and filtrated, the resulting solution was concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=1/1) to yield the intermediate ether (30 mg, 11%). This was taken up in anhydrous dichloromethane (20 mL). The mixture was cooled to −78° C., trifluoroborane (1 mL) was added drop-wise to the mixture and the mixture was stirred at −78° C. for 2 h, 1 h at room temperature and at reflux for 1 h. The mixture was poured into water (20 mL), extracted with dichloromethane (3×20 mL), the organic layers was combined, dried over anhydrous sodium sulphate, filtrated and concentrated. The residue was purified by silica gel column chromatography (eluting with ethyl acetate/petroleum ether=½) to yield the title compound (20 mg, 69%). 1H NMR (300 MHz, CDCl3): 7.29-7.13 (m, 4H), 7.10-6.86 (m, 5H), 4.38 (q, 2H, J=8.1 Hz), 3.79-3.26 (m, 6H), 3.08-2.92 (m, 2H), 2.27-1.92 (m, 2H). LC-MS: [M+1]+=407.2.

Workup

  1. temperaturewas refluxed overnight under nitrogen atmosphere
  2. temperatureThe mixture was cooled
  3. filtrationfiltrated
  4. concentrationthe resulting solution was concentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=1/1)
  6. customto yield the intermediate ether (30 mg, 11%)
  7. temperatureat reflux for 1 h
  8. extractionextracted with dichloromethane (3×20 mL)
  9. dry with materialdried over anhydrous sodium sulphate
  10. filtrationfiltrated
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel column chromatography (eluting with ethyl acetate/petroleum ether=½)

Sources & evidence

ORD record
ord-8923cddc2c70421a861ecfed1b2f597b
Source dataset
uspto-grants-2013_08
Patent number
US08501768B2

Reaction notes

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