Hydrochloric Acid → 4-(2-(2-Carboxy-ethyl)-3-{6-[3'-fluoro-5-(piperazine-1-carbonyl)-biphenyl-3-yloxy]-hexyl}-phenoxy)-butyric Acid

HRID 1670092Notes

Reaction equation

HRID 1670092 reaction equation
C([O:3][C:4]([CH2:6][CH2:7][C:8]1[C:13]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]1[CH:31]=[C:32]([C:43]([OH:45])=O)[CH:33]=[C:34]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=2)[CH:35]=1)=[O:5])C.C(OC([N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)=O)(C)(C)C.C1CN([P+](Br)(N2CCCC2)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:4]([CH2:6][CH2:7][C:8]1[C:9]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]2[CH:35]=[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=3)[CH:33]=[C:32]([C:43]([N:53]3[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]3)=[O:45])[CH:31]=2)=[CH:10][CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])([OH:3])=[O:5]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733179PyBroPHCID 67338077HCID 67338077, compound

Product 1

HCID 426436304-(2-(2-Carboxy-ethyl)-3-{6-[3'-fluoro-5-(piperazine-1-carbonyl)-biphenyl-3-yloxy]-hexyl}-phenoxy)-butyric Acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-{6-[2-(2-Ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-3′-fluoro-biphenyl-3-carboxylic acid (150 mg), piperazine-1-carboxylic acid tert-butyl ester (54 mg), PyBroP (130 mg), diisopropylethylamine (85 □l) and dichloromethane (3 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 total amount of the product obtained from the previous step was dissolved in ethanol (2 mL) and 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, concentrated to dryness, redissolved in a mixture of TFA and dichloromethane (1:1, 2 mL) and stirred at room temperature for 3 h. The solvents were removed under reduced pressure and the title compound was purified on reverse-phase HPLC.

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 total amount of the product obtained from the previous step
  6. customThe resulting reaction mixture
  7. stirringwas stirred at room temperature for 5 h
  8. extractionextracted into ethyl acetate
  9. extractionThe organic extract
  10. dry with materialwas dried over anhydrous sodium sulfate
  11. concentrationconcentrated to dryness
  12. dissolutionredissolved in a mixture of TFA and dichloromethane (1:1, 2 mL)
  13. stirringstirred at room temperature for 3 h
  14. customThe solvents were removed under reduced pressure
  15. customthe title compound was purified on reverse-phase HPLC

Sources & evidence

ORD record
ord-0c0a2a6900fc42eba70e1fa4170e1e73
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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