Ammonium Hydroxide → HCID 23289880, compound

HRID 366772Notes

Reaction equation

HRID 366772 reaction equation
[Br:1]Br.N[C:4]1[CH:5]=[C:6]2[CH2:14][O:13][C:12]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=3[C:10](=[C:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22][CH2:21]3)[C:7]2=[N:8][CH:9]=1.N([O-])=O.[Na+].[OH-].[NH4+]>Br.O>[Br:1][C:4]1[CH:5]=[C:6]2[CH2:14][O:13][C:12]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=3[C:10](=[C:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22][CH2:21]3)[C:7]2=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 24408BromineHCID 23289895HCID 23289895, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 23289880HCID 23289880, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Bromine (1.0 ml, 19.4 mmol) was added to a suspension of ethyl 4-(3-amino-8-chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)-1-piperidine-carboxylate (1.5 g, 3.75 mmol) in hydrobromic acid (150 ml) at 0° C. for 10 minutes. Sodium nitrite (0.7 g, 10.14 mmol) in water (5 ml) was added at 0° C., and the mixture was stirred at 0° C. for 1 hour and then at 20° C. for 2 hours. The reaction mixture was poured onto ice (200 g), basified with concentrated ammonium hydroxide and extracted with ethyl acetate (500 ml). The organic layer was washed with water (300 ml), dried (MgSO4), filtered and evaporated, yielding a crude product which was chromatographed on silica gel and eluted with 30%ethylacetate/hexanes. The product was recrystallized from ether to afford a white powder, ethyl 4-(3-bromo-8-chloro-5,11-dihydro[1]benz-oxepino[4,3-b]pyridin-11-ylidene)-1-piperidine-carboxylate (1.0 g, 58%), m.p. 148-149° C. MS (CI, M+H)=463; anal.: found: C, 53.92; H, 4.16; N, 6.18; C21H20BrClN2O3 requires: C, 54.38; H, 4.34; N, 6.04.

Workup

  1. waitat 20° C. for 2 hours
  2. additionThe reaction mixture was poured onto ice (200 g)
  3. extractionextracted with ethyl acetate (500 ml)
  4. washThe organic layer was washed with water (300 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customyielding a crude product which
  9. customwas chromatographed on silica gel
  10. washeluted with 30%ethylacetate/hexanes
  11. customThe product was recrystallized from ether

Sources & evidence

ORD record
ord-ad12bce8c1024fbbae79712f496f6950
Source dataset
uspto-grants-2000_10
Patent number
US06130229

Reaction notes

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