Hydrochloric Acid → HCID 9803546, compound

HRID 1069101Notes

Reaction equation

HRID 1069101 reaction equation
Cl.Cl.C[O:4][C:5]([C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][CH2:20][CH2:21][NH:22][CH2:23][C@@H:24]([C:26]3[CH:31]=[C:30]([Cl:32])[CH:29]=[C:28]([Cl:33])[CH:27]=3)[OH:25])[CH:14]=2)[CH:10]=[CH:11][CH:12]=1)=[O:6].O.[OH-].[Li+].Cl>CO.O>[Cl:32][C:30]1[CH:31]=[C:26]([C@@H:24]([OH:25])[CH2:23][NH:22][CH2:21][CH2:20][NH:19][C:15]2[CH:14]=[C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([C:5]([OH:6])=[O:4])[CH:8]=3)[CH:18]=[CH:17][CH:16]=2)[CH:27]=[C:28]([Cl:33])[CH:29]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrate2×HCID 69779496HCID 69779496, compound

Product 1

HCID 9803546HCID 9803546, compoundYield 16.9%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A crude sample of (R)-3′-[[2-[[2-(3,5-dichlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-[1,1′-biphenyl]-3-carboxylic acid methyl ester dihydrochloride (from Example 8, 557 mg), was treated with lithium hydroxide monohydrate (220 mg) in 3:1 methanol/water (28 mL) and stirred for 1 day. Additional lithium hydroxide monohydrate (22 mg) was added and the mixture was stirred overnight. The mixture was treated with 0.5 N aq. HCl until approximately pH6, and the resulting solid (400 mg) was collected by suction filtration. Silica gel chromatography (eluting with 6:2:0.1 chloroform/methanol/ammonium hydroxide) gave a solid that was triturated with hexanes. This material was treated with 1 N aqueous HCl, and the solid was washed by stirring with ethyl acetate. The solid was dried in vacuo to give the title compound (78.6 mg).

Workup

  1. stirringthe mixture was stirred overnight
  2. filtrationthe resulting solid (400 mg) was collected by suction filtration
  3. washSilica gel chromatography (eluting with 6:2:0.1 chloroform/methanol/ammonium hydroxide)
  4. customgave a solid
  5. customthat was triturated with hexanes
  6. additionThis material was treated with 1 N aqueous HCl
  7. washthe solid was washed
  8. stirringby stirring with ethyl acetate
  9. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-ed83df9c57b14722b4f4406c71a8427b
Source dataset
uspto-grants-2001_06
Patent number
US06251925B1

Reaction notes

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