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Hydrogen Peroxide → 1,3-Dichloro-7,8,9,10-tetrahydro-6,10-methanoazepino[2,1-b]quinazolin-12(6H)-one

HRID 375612
Notes
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Reaction equation

HRID 375612 reaction equation
[CH:1]12[CH2:9][CH:5]([NH:6][C:7]1=O)[CH2:4][CH2:3][CH2:2]2.P(Cl)(Cl)(Cl)=O.[Cl:15][C:16]1[CH:17]=[C:18]([NH2:26])[C:19](=[C:23]([Cl:25])[CH:24]=1)[C:20](O)=[O:21].N1C2C(=CC=CC=2)C(=O)C1=O.OO.ClC1C=CC=C(C(O)=O)C=1N.C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)Cl.C(N(CC)CC)C>[Cl:25][C:23]1[CH:24]=[C:16]([Cl:15])[CH:17]=[C:18]2[C:19]=1[C:20](=[O:21])[N:6]1[CH:5]3[CH2:9][CH:1]([CH2:2][CH2:3][CH2:4]3)[C:7]1=[N:26]2
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 7

HCID 784Hydrogen PeroxideHCID 7054IsatinHCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 808072-Amino-3-chlorobenzoic acidHCID 2904984,6-Dichloroanthranilic acidHCID 12209229HCID 12209229, compound

Product 1

HCID 189926121,3-Dichloro-7,8,9,10-tetrahydro-6,10-methanoazepino[2,1-b]quinazolin-12(6H)-one

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 3.82 g of 6-azabicyclo[3,2,1]-octan-7-one (R. L. Augustine and L. A. Bag, J. Org. Chem., 40:1074 (1975)) in 25 mL of chloroform was added 4 mL of phosphorus oxychloride. After the mildly exothermic reaction ceased, the mixture was stirred at room temperature for 4 hours. 6.3 g of 4,6-dichloroanthranilic acid (prepared from the corresponding isatine: T. Sandmeyer, Helv. Chim. Acta, 2:234 (1919), by oxidation with alkaline hydrogen peroxide, following the procedure described by Baker, et al., J. Org. Chem., 17:141 (1952) for the synthesis of 3-chloroanthranilic acid) was dissolved in a mixture of 50 mL of chloroform and 10 mL of triethylamine. This solution was added to the stirred above solution of the imidoyl chloride at such a rate as to prevent boiling over (exothermic!), approximately 2 minutes. Then the mixture was stirred at room temperature for 4 hours and then refluxed for 3 days. Then the dark brown mixture was treated with 200 mL of 10% aqueous K2CO3. The chloroform layer was separated, aqueous layer was extracted two times with 50 mL of chloroform. The combined chloroform extract was dried with anhydrous potassium carbonate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, using 8:1 chloroform-ethyl acetate as eluent. The corresponding fractions were concentrated in vacuo, giving a crystalline solid. This was recrystallized from ethyl acetate-hexane, giving colorless crystals.

Workup

  1. customAfter the mildly exothermic reaction
  2. additionThis solution was added to the
  3. customover (exothermic!), approximately 2 minutes
  4. stirringThen the mixture was stirred at room temperature for 4 hours
  5. temperaturerefluxed for 3 days
  6. customThe chloroform layer was separated
  7. extractionaqueous layer was extracted two times with 50 mL of chloroform
  8. extractionThe combined chloroform extract
  9. dry with materialwas dried with anhydrous potassium carbonate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was chromatographed on silica gel
  13. concentrationThe corresponding fractions were concentrated in vacuo
  14. customgiving a crystalline solid
  15. customThis was recrystallized from ethyl acetate-hexane
  16. customgiving colorless crystals

Sources & evidence

ORD record
ord-d1fb9e5838a84819aec85408c77daf62
Source dataset
uspto-grants-1996_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05486512

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes