1,1-Dichloroethane → 8-(Benzyloxy)-N-(4-((3-methyloxetan-3-YL)methoxy)-2-nitrophenyl)quinolin-2-amine

HRID 351305Notes

Reaction equation

HRID 351305 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16](O)[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][C:21]1([CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[C:29]([N+:34]([O-:36])=[O:35])[CH:28]=2)[CH2:24][O:23][CH2:22]1.C(=O)([O-])[O-].[Cs+].[Cs+].ClC(Cl)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([NH:33][C:30]1[CH:31]=[CH:32][C:27]([O:26][CH2:25][C:21]3([CH3:20])[CH2:22][O:23][CH2:24]3)=[CH:28][C:29]=1[N+:34]([O-:36])=[O:35])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 63651,1-DichloroethaneHCID 10796Cesium carbonateHCID 184359014-((3-Methyloxetan-3-yl)methoxy)-2-nitroanilineHCID 178515619HCID 178515619, compound

Product 1

HCID 114769578-(Benzyloxy)-N-(4-((3-methyloxetan-3-YL)methoxy)-2-nitrophenyl)quinolin-2-amineYield 77%

Reagents, catalysts & solvents 3

HCID 742671,2-Bis(diphenylphosphino)ethaneCatalystHCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The compound, 8-Benzyloxy-quinolin-2-ol (5 g, 18.5 m,mol, 1.0 equivalent), 4-(3-Methyl-oxetan-3-ylmethoxy)-2-nitro-phenylamine (5.3 g, 22.2 mmol, 1.2 equivalents), cesium carbonate (8.46 g, 26 mmol, 1.4 equivalents), DIPHOS (1,2-Bis(diphenylphosphino)ethane; 443 mg, 111 μmol, 0.06 equivalents) and toluene (75 mL, 15 volumes) were charged to a 100 mL round bottom flask. The reaction was deoxygenated. Palladium acetate (83 mg, 37 μmol, 0.02 equivalents) was added and the reaction was deoxygenated again. The reaction was heated to 100° C. for 24–30 hours. At reaction completion, the reaction was cooled to 55° C. and dichloroethane (“DCE”; 75 mL, 15 volumes) was charged. The slurry was filtered through a pad of Celite and then the flask and filter were rinsed once with additional DCE.(50 mL, 10 volumes). The organics were concentrated to low volume and ethyl acetate (50 mL, 10 volumes) was added. The reaction was heated to reflux and allowed to cool to 20–25° C. The solids were granulated for 10–20 hours, filtered, and dried under vacuum at 40° C. with a slight nitrogen bleed to yield 6.72 g (8-Benzyloxy-quinolin-2-yl)-[4-(3-methyl-oxetan-3-ylmethoxy)-2-nitro-phenyl]-amine as an orange solid (77% yield). The material was judged to be about 95% pure by NMR, with ˜5% of the DIPHOS bis-oxide.

Workup

  1. customThe reaction was deoxygenated
  2. customthe reaction was deoxygenated again
  3. customAt reaction completion
  4. temperaturethe reaction was cooled to 55° C.
  5. filtrationThe slurry was filtered through a pad of Celite
  6. filtrationthe flask and filter
  7. washwere rinsed once with additional DCE
  8. concentrationThe organics were concentrated to low volume and ethyl acetate (50 mL, 10 volumes)
  9. additionwas added
  10. temperatureThe reaction was heated
  11. temperatureto reflux
  12. temperatureto cool to 20–25° C
  13. waitThe solids were granulated for 10–20 hours
  14. filtrationfiltered
  15. customdried under vacuum at 40° C. with a slight nitrogen

Sources & evidence

ORD record
ord-22b82e19aa7a4ecbbc3c86a35fef6561
Source dataset
uspto-grants-2007_02
Patent number
US07183414B2

Reaction notes

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