Bromoacetyl bromide → HCID 67767694, compound

HRID 361584Notes

Reaction equation

HRID 361584 reaction equation
[CH2:1]([N:8]([CH3:34])[C:9](=[O:33])[NH:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:22](=[O:23])[C@H:21]3[CH2:24][CH2:25][CH2:26][C@H:20]3[NH:19][C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]2=3)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:36][C:37](Br)=[O:38].C([O-])(O)=O.[Na+].[C:45]1(=[O:55])[NH:49][C:48](=[O:50])[C:47]2=[CH:51][CH:52]=[CH:53][CH:54]=[C:46]12.[K]>ClCCl.O>[CH2:1]([N:8]([CH3:34])[C:9](=[O:33])[NH:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:22](=[O:23])[C@H:21]3[CH2:24][CH2:25][CH2:26][C@H:20]3[N:19]([C:37](=[O:38])[CH2:36][N:49]3[C:48](=[O:50])[C:47]4=[CH:51][CH:52]=[CH:53][CH:54]=[C:46]4[C:45]3=[O:55])[C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]2=3)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 61147Bromoacetyl bromideHCID 516892Sodium BicarbonateHCID 24194345Phthalimide potassium saltHCID 67767615HCID 67767615, compound

Product 1

HCID 67767694HCID 67767694, compoundYield 17.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (3aR*,10aS*)-9-[4-(3-benzyl-3-methylureido)benzyl]-2,3,3a,4,9,10a-hexahydrobenzo[b]-cyclopenta[e][1,4]diazepin-10(1H)-one (0.30 g, 0.66 mmol) in dichloromethane (5 mL) was added bromoacetyl bromide (58 μL, 0.67 mmol) and the mixture was stirred at room temperature for 30 minutes. After addition of saturated aqueous NaHCO3 solution, the aqueous layer was separated and extracted with dichloromethane. The pooled organic layer was washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane-ethyl acetate=1:11:2) to recover an amorphous fraction containing (3aR*,10aS*)-9-[4-(3-benzyl-3-methylureido)benzyl]-4-(bromoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo[b]-cyclopenta[e][1,4]diazepin-10(1H)-one. This amorphous fraction was dissolved in DMF (1.5 mL) and after addition of potassium phthalimide (93 mg, 0.5 mmol), the solution was stirred at room temperature for 1.5 hours. This reaction mixture was diluted with water and extracted with 3 portions of ethyl acetate. The pooled organic layer was washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=2:11:11:2) and crystallized from ethyl acetate-diethyl ether to provide 57 mg (yield 13%) of the title compound. m.p. 156°-158° C.

Workup

  1. customthe aqueous layer was separated
  2. extractionextracted with dichloromethane
  3. washThe pooled organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto recover an amorphous fraction
  8. additioncontaining (3aR*,10aS*)-9-[4-(3-benzyl-3-methylureido)benzyl]-4-(bromoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo[b]-cyclopenta[e][1,4]diazepin-10(1H)-one
  9. dissolutionThis amorphous fraction was dissolved in DMF (1.5 mL)
  10. stirringthe solution was stirred at room temperature for 1.5 hours
  11. extractionextracted with 3 portions of ethyl acetate
  12. washThe pooled organic layer was washed with water
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate=2:11:11:2)
  17. customcrystallized from ethyl acetate-diethyl ether

Sources & evidence

ORD record
ord-67388bd09632407182ff1efdb6e16625
Source dataset
uspto-grants-1999_02
Patent number
US05866567

Reaction notes

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