Hexahydro-1,4-diazepine → 8-(1,4-Diazepan-1-yl)-7-methoxyquinoline

HRID 532829Notes

Reaction equation

HRID 532829 reaction equation
Br[C:2]1[C:3]([OH:12])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[NH:13]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.[CH3:20]C(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[N:13]1([C:2]2[C:3]([O:12][CH3:20])=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 68163Hexahydro-1,4-diazepineHCID 23676156Sodium t-butoxideHCID 1358901048-Bromo-7-hydroxyquinoline

Product 1

HCID 593661628-(1,4-Diazepan-1-yl)-7-methoxyquinolineYield 78%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 8-bromo-7-hydroxyquinoline (126 g, 0.488 mol), homopiperazine (201 g, 2.0 mol), (±)-BINAP (19.8 g, 31.8 mmol), and sodium tert-butoxide (75.6 g, 0.786 mol) was suspended in 900 mL of toluene and purged with nitrogen gas for an hour. Tris-benzylidineacetone dipalladium(0) (9.7 g, 10.6 mmol) was added. The mixture was purged for another hour, heated to reflux under nitrogen for 4 hr, cooled to rt, carefully diluted with 1300 mL of 20% AcOH in water and filtered through 100 g of celite. The celite pad was washed with 20% AcOH in water (1 L×2) and ethyl acetate (1 L×1). The aqueous phase was extracted with ethyl acetate (1 L×4), adjusted to pH 10-11 with NaOH (10 N, 500 mL), and then extracted with a mixture of CH2Cl2 and iPrOH (80:20, 1 L×2 and 0.5 L×4). The combined organic phase was washed with saline (400 mL), dried over Mg2SO4 and evaporated to give the desired product (98 g).

Workup

  1. custompurged with nitrogen gas for an hour
  2. customThe mixture was purged for another hour
  3. temperatureheated
  4. temperatureto reflux under nitrogen for 4 hr
  5. additioncarefully diluted with 1300 mL of 20% AcOH in water
  6. filtrationfiltered through 100 g of celite
  7. washThe celite pad was washed with 20% AcOH in water (1 L×2) and ethyl acetate (1 L×1)
  8. extractionThe aqueous phase was extracted with ethyl acetate (1 L×4)
  9. extractionextracted with a mixture of CH2Cl2 and iPrOH (80:20, 1 L×2 and 0.5 L×4)
  10. washThe combined organic phase was washed with saline (400 mL)
  11. dry with materialdried over Mg2SO4
  12. customevaporated

Sources & evidence

ORD record
ord-2b6aae76b900467ba8d9d1c496814e01
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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