Hydrochloric Acid → HCID 178429009, compound

HRID 1620137Notes

Reaction equation

HRID 1620137 reaction equation
C[O:2][C:3](=[O:39])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:25](=[O:38])[CH:26]([NH2:37])[CH2:27][C:28]2[C:33]([CH3:34])=[CH:32][C:31]([OH:35])=[CH:30][C:29]=2[CH3:36])[CH:12]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:18]=2)[CH3:13])=[CH:6][CH:5]=1.[Li+].[OH-].Cl>C1COCC1>[NH2:37][CH:26]([CH2:27][C:28]1[C:33]([CH3:34])=[CH:32][C:31]([OH:35])=[CH:30][C:29]=1[CH3:36])[C:25]([N:11]([CH2:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:39])=[O:2])=[CH:5][CH:6]=1)[CH:12]([C:14]1[NH:15][CH:16]=[C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:18]=1)[CH3:13])=[O:38]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 178497941HCID 178497941, compound

Product 1

HCID 178429009HCID 178429009, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-({[2-amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-benzoic acid methyl ester (TFA salt), (0.043 g, 0.067 mmol) in 5 mL of THF was cooled in an ice bath. A cold (5-10° C.) 3M aqueous solution of LiOH (5 mL) was added and the reaction mixture was stirred vigorously while cold. Chilled (5-10° C.) 2M aqueous HCl (7.5 mL) was added dropwise to neutralize the mixture was stirred for 5 min, and then partially concentrated in vacuo unheated. The resultant aqueous suspension was extracted seven times with EtOAc. The extracts were dried over Na2SO4, filtered, and concentrated to afford 0.030 g of 4-({[2-amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-benzoic acid as a white powder. The material was taken up in EtOH and treated with 1M HCl in Et2O. The solution was concentrated and the residue was triturated with CH3CN. A 0.021 g (53%) sample of 4-({[2-amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-benzoic acid was collected as its HCl salt. MS (ES+) (relative intensity): 513.2 (100) (M+1).

Workup

  1. additionwas added dropwise
  2. stirringwas stirred for 5 min
  3. concentrationpartially concentrated in vacuo unheated
  4. extractionThe resultant aqueous suspension was extracted seven times with EtOAc
  5. dry with materialThe extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d817dc5ed00a4dfe804a2f6fe3f073de
Source dataset
uspto-grants-2014_07
Patent number
US08772325B2

Reaction notes

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