Hydrochloric Acid → 3-(5-(5-Chloro-2-(((4'-fluoro-3'-methyl-[1,1'-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoic acid

HRID 405227Notes

Reaction equation

HRID 405227 reaction equation
[Li+].[OH-].[CH2:3]1COCC1.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[C:41](F)[CH:40]=3)=[CH:35][CH:34]=2)=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([NH:23][CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])=[O:22])=[N:19][CH:20]=2)[CH:14]=1.Cl>C(Cl)Cl.O.CO>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[C:41]([CH3:3])[CH:40]=3)=[CH:35][CH:34]=2)=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([NH:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:22])=[N:19][CH:20]=2)[CH:14]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 71059933Ethyl 3-(5-(5-chloro-2-(((3',4'-difluoro-[1,1'-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoate

Product 1

HCID 710599243-(5-(5-Chloro-2-(((4'-fluoro-3'-methyl-[1,1'-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A 1M aqueous solution of LiOH (2.0 mL, 2.0 mmol) was added to a THF (2.0 mL) and MeOH (0.5 mL) solution of ethyl 3-(5-(5-chloro-2-(((3′,4′-difluoro-[1,1′-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoate (32 mg, 0.06 mmol) and the resulting mixture was stirred at room temperature. After 1 h the resulting mixture was neutralized with 2M aqueous HCl, diluted with DCM and water and the layers were separated. The aqueous layer was extracted with DCM and the combined extracts were dried (Na2SO4), and concentrated. The product was dissolved in Et2O (5-7 mL) and then added to heptane (25 mL). The resulting mixture was contracted slowly to about half volume (15 mL). The solid was collected by filtration, washed with heptane (3 mL×2) and dried in vacuo to yield the title compound.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with DCM
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe product was dissolved in Et2O (5-7 mL)
  6. additionadded to heptane (25 mL)
  7. filtrationThe solid was collected by filtration
  8. washwashed with heptane (3 mL×2)
  9. customdried in vacuo

Sources & evidence

ORD record
ord-ef65b46fd0c44e33819e6ea725c4bcd6
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

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