Benzaldehyde → HCID 86703964, compound

HRID 1773886Notes

Reaction equation

HRID 1773886 reaction equation
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[CH:3]=1.[Li][CH2:25][CH2:26][CH2:27][CH3:28].[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])(O)=O.[Na+].[Mn]([O-])([O-])(=O)=O.[Ba+2].[CH2:48]1COC[CH2:49]1>O1CCOCC1.O=[Mn]=O.O>[CH3:19][N:16]1[CH2:17][CH2:18][CH:13]([O:12][CH:9]2[C:8]3[CH:20]=[CH:21][CH:22]=[CH:23][C:7]=3[CH2:6][CH2:5][N:4]3[C:10]2=[N:11][C:2]([C:25]2[CH:49]=[CH:48][C:28]([C:29]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:36])=[CH:27][CH:26]=2)=[CH:3]3)[CH2:14][CH2:15]1

Participants

10

Reactant 6

HCID 240BenzaldehydeHCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 3084030Barium manganateHCID 726957782-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azuleneHCID 178418339Butyllithium

Product 1

HCID 86703964HCID 86703964, compound

Reagents, catalysts & solvents 3

HCID 14801Manganese dioxideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (200 mg, 0.47 mmoles) in THF (2.6 mL) in a screw-capped vial under argon at −78° C. is added 2.3M nBuLi (0.44 mL, 0.94 mmole). The reaction mixture is stirred at −78° C. for 30 min. Benzaldehyde (96 μL, 1.03 mmole) is added. The reaction mixture is allowed to reach room temperature. Water and a NaHCO3 saturated solution are added, and the aqueous phase is extracted three times with AcOEt. The organic phase is washed with water, brine, dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (98:2:0.2) to (95:5:0.5). The residue (130 mg, 0.285 mmole) is dissolved in 1,4-dioxane (1.4 mL) and barium manganate (73 mg, 0.285 mmole) as well as MnO2 (100 mg, 1.14 mmole) are added. The reaction mixture is heated at 80° C. for 24 h. The reaction mixture is filtered over celite, cake washed with MeOH. The solvents are removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (98:2:0.2) to (96.5:3.5:0.35) to give {4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-phenyl-methanone.

Workup

  1. customto reach room temperature
  2. extractionthe aqueous phase is extracted three times with AcOEt
  3. washThe organic phase is washed with water, brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by silica gel chromatography
  8. temperatureThe reaction mixture is heated at 80° C. for 24 h
  9. filtrationThe reaction mixture is filtered over celite, cake
  10. washwashed with MeOH
  11. customThe solvents are removed under reduced pressure
  12. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-9b99da4faf3e474193a904099974a549
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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