Hydrochloric Acid → (2S,4S)-4-(2-Hydroxycarbamoyl-4-methylpentanoylamino)-1-{pentyl[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]carbamoyl}pyrrolidine-2-carboxylic Acid

HRID 425133Notes

Reaction equation

HRID 425133 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([NH:10][C:11](=[O:27])[CH:12]([C:17](=[O:26])[NH:18][O:19]C(=O)C(C)(C)C)[CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:7][N:6]1[C:28](=[O:53])[N:29]([CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[C:43]2[NH:47][N:46]=[N:45][N:44]=2)=[CH:33][CH:32]=1)=[O:4].[OH-].[Na+].Cl>CO>[OH:19][NH:18][C:17]([CH:12]([CH2:13][CH:14]([CH3:15])[CH3:16])[C:11]([NH:10][C@@H:8]1[CH2:7][N:6]([C:28](=[O:53])[N:29]([CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[CH2:30][C:31]2[CH:32]=[CH:33][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]3[NH:47][N:46]=[N:45][N:44]=3)=[CH:35][CH:36]=2)[C@H:5]([C:3]([OH:4])=[O:2])[CH2:9]1)=[O:27])=[O:26]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178446312HCID 178446312, compound

Product 1

HCID 178446311(2S,4S)-4-(2-Hydroxycarbamoyl-4-methylpentanoylamino)-1-{pentyl[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]carbamoyl}pyrrolidine-2-carboxylic AcidYield 34.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(2S,4S)-4-[2-(2,2-Dimethylpropionyloxycarbamoyl)-4-methylpentanoylamino]-1-{pentyl[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]carbamoyl}pyrrolidine-2-carboxylic acid methyl ester (2.2 g, 3 mmol) was dissolved in MeOH (20 mL). An aqueous solution of NaOH (1M, 10 ml; 10M, 1 mL) was added, and the mixture was stirred at room temperature for 15 minutes. The solution was acidified with HCl and extracted (EtOAc, 2×50 mL). The combined organics were washed with saturated aqueous NaCl (50 mL), dried over Na2SO4, and the solvent evaporated. The residue was purified by reverse phase preparative HPLC (twice) to afford the title compound (657 mg, 1.03 mmol). MS m/z: [M+H]+ calcd for C32H42N8O6, 634.7. found 635.3.

Workup

  1. extractionextracted (EtOAc, 2×50 mL)
  2. washThe combined organics were washed with saturated aqueous NaCl (50 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent evaporated
  5. customThe residue was purified by reverse phase preparative HPLC (twice)

Sources & evidence

ORD record
ord-f436ab6c333a46949d22d81735acd1f6
Source dataset
uspto-grants-2012_01
Patent number
US08106082B2

Reaction notes

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