Hydrochloric Acid → 4-(2-(2-Carboxy-ethyl)-3-{6-[3-cyclopropylcarbamoyl-5-(4-methyl-thiophen-3-yl)-phenoxy]-hexyl}-phenoxy)-butyric acid

HRID 1670101Notes

Reaction equation

HRID 1670101 reaction equation
C(OC(CCC1C(OCCCC(OCC)=O)=CC=CC=1CCCCCCOC1C=C([CH:36]=[C:37]([C:39]2[C:43]([CH3:44])=[CH:42][S:41][CH:40]=2)[CH:38]=1)C(O)=O)=O)C.O1C2C=CC(C3C=[C:57]([CH:61]=[C:62]([O:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][C:71]4[CH:76]=[CH:75][CH:74]=[C:73]([O:77][CH2:78][CH2:79][CH2:80][C:81]([O:83]CC)=[O:82])[C:72]=4[CH2:86][CH2:87][C:88]([O:90]CC)=[O:89])C=3)[C:58]([OH:60])=O)=CC=2OCC1.C1CN([P+](Br)([N:104]2[CH2:108][CH2:107][CH2:106]C2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[OH-].[Na+].Cl>C(OCC)(=O)C.C(O)C.ClCCl>[C:88]([CH2:87][CH2:86][C:72]1[C:71]([CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][O:64][C:62]2[CH:38]=[C:37]([C:39]3[C:43]([CH3:44])=[CH:42][S:41][CH:40]=3)[CH:36]=[C:57]([C:58](=[O:60])[NH:104][CH:108]3[CH2:106][CH2:107]3)[CH:61]=2)=[CH:76][CH:75]=[CH:74][C:73]=1[O:77][CH2:78][CH2:79][CH2:80][C:81]([OH:83])=[O:82])([OH:90])=[O:89]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 673380073-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-benzoic AcidHCID 673382323-{6-[2-(2-Ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-5-(4-methyl-thiophen-3-yl)-benzoic Acid

Product 1

HCID 426438864-(2-(2-Carboxy-ethyl)-3-{6-[3-cyclopropylcarbamoyl-5-(4-methyl-thiophen-3-yl)-phenoxy]-hexyl}-phenoxy)-butyric acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The acid component, 3-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-5-(4-methyl-thiophen-3-yl)-benzoic acid or 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-benzoic acid (0.15 mmol), the appropriate amine (1.2 eq.), PyBroP (1.1 eq.), diisopropylethylamine (2 eq.) and dichloromethane (2 mL) were combined together and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate and concentrated to dryness. The material was used without further purification for the next step. The total amount of the product obtained from the previous step was dissolved in ethanol (2 mL) and a 10 M NaOH solution was added (3 eq.). The resulting reaction mixture was stirred at room temperature for 5 h. Then it was neutralized with 3 N HCl and extracted into ethyl acetate. The organic extract was dried over anhydrous sodium sulfate and concentrated to dryness. The crude material was purified on reverse-phase HPLC to afford the title compound.

Workup

  1. washwashed with water and brine
  2. extractionThe organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe material was used without further purification for the next step
  6. customThe total amount of the product obtained from the previous step
  7. customThe resulting reaction mixture
  8. stirringwas stirred at room temperature for 5 h
  9. extractionextracted into ethyl acetate
  10. extractionThe organic extract
  11. dry with materialwas dried over anhydrous sodium sulfate
  12. concentrationconcentrated to dryness
  13. customThe crude material was purified on reverse-phase HPLC

Sources & evidence

ORD record
ord-c0d18ecaa46049ed8d32c77400e7010c
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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