Hydrochloric Acid → 4-[3-{6-[3-Benzo[1,3]dioxol-5-yl-5-(5-oxo-[1,4]diazepane-1-carbonyl)-phenoxy]-hexyl}-2-(2-carboxy-ethyl)-phenoxy]-butyric Acid

HRID 1670080Notes

Reaction equation

HRID 1670080 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:11]=[C:12]([CH:23]=[C:24]([OH:26])[CH:25]=3)[C:13]([N:15]3[CH2:21][CH2:20][C:19](=[O:22])[NH:18][CH2:17][CH2:16]3)=[O:14])=[CH:9][C:4]=2[O:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].C([O:35][C:36](=[O:61])[CH2:37][CH2:38][CH2:39][O:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]Br)[C:42]=1[CH2:54][CH2:55][C:56]([O:58]CC)=[O:57])C.Cl>CC(C)=O.CN(C=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:25]=[C:24]([CH:23]=[C:12]([C:13]([N:15]4[CH2:21][CH2:20][C:19](=[O:22])[NH:18][CH2:17][CH2:16]4)=[O:14])[CH:11]=3)[O:26][CH2:52][CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][C:43]3[C:42]([CH2:54][CH2:55][C:56]([OH:58])=[O:57])=[C:41]([CH:46]=[CH:45][CH:44]=3)[O:40][CH2:39][CH2:38][CH2:37][C:36]([OH:61])=[O:35])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 575864914-[3-(6-Bromo-hexyl)-2-(ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterHCID 57905898HCID 57905898, compound

Product 1

HCID 673400914-[3-{6-[3-Benzo[1,3]dioxol-5-yl-5-(5-oxo-[1,4]diazepane-1-carbonyl)-phenoxy]-hexyl}-2-(2-carboxy-ethyl)-phenoxy]-butyric Acid

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 1-(3-benzo[1,3]dioxol-5-yl-5-hydroxy-benzoyl)-[1,4]diazepan-5-one (0.58 mmol) in a mixture of acetone and DMF (2:1, 2 mL) were added potassium carbonate (10 eq.) and 4-[3-(6-bromo-hexyl)-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (1.1 eq). The resulting mixture was stirred at 75° C. for 2 days. Then the insoluble material was filtered out and the filtrate was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate, concentrated and used for the next step without further purification. The total amount of material from the previous step was dissolved in 1,2-dichloroethane (4 mL), followed by addition of trimethyltin hydroxide (433 mg). The resulting reaction mixture was stirred at 70° C. for 7 days. Then it was neutralized with 5% HCl and extracted into ethyl acetate. The organic extract was washed with water and brine and dried over anhydrous sodium sulfate. The crude material was purified by reverse-phase HPLC to yield the title compound.

Workup

  1. filtrationThen the insoluble material was filtered out
  2. additionthe filtrate was diluted with ethyl acetate
  3. washwashed with water and brine
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customused for the next step without further purification
  8. dissolutionThe total amount of material from the previous step was dissolved in 1,2-dichloroethane (4 mL)
  9. additionfollowed by addition of trimethyltin hydroxide (433 mg)
  10. customThe resulting reaction mixture
  11. stirringwas stirred at 70° C. for 7 days
  12. extractionextracted into ethyl acetate
  13. extractionThe organic extract
  14. washwas washed with water and brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. customThe crude material was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-2715fd5ba03344bb96239706d6e910ca
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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