Hydrochloric Acid → (S)-5-(biphenyl-4-yl)-4-(phosphonomethylamino)-2-pentenoic acid

HRID 1655288Notes

Reaction equation

HRID 1655288 reaction equation
C([O:3][C:4](=[O:29])[CH:5]=[CH:6][C@@H:7]([NH:21][CH2:22][P:23]([O:27]C)([O:25]C)=[O:24])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].Cl.C[Si](Br)(C)C>CO>[C:12]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:11]=[CH:10][C:9]([CH2:8][C@H:7]([NH:21][CH2:22][P:23]([OH:27])([OH:25])=[O:24])[CH:6]=[CH:5][C:4]([OH:29])=[O:3])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 76113BromotrimethylsilaneHCID 53707898(S)-5-(Biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester

Product 1

HCID 54035155(S)-5-(biphenyl-4-yl)-4-(phosphonomethylamino)-2-pentenoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(S)-5-(Biphenyl-4-yl)-4-[(dimethylphosphonomethyl)-amino]-2-pentenoic acid ethyl ester (536 mg, 1.28 mmol) is dissolved in methanol (1 mL) and treated with 1N sodium hydroxide (2 mL, 2 mmol). The reaction mixture is stirred for 3 hours at room temperature, then 1N hydrochloric acid (5 mL) is added. The carboxylic acid is extracted in methylene chloride (20 mL). The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is suspended in methylene chloride (2 mL) under nitrogen and treated with trimethylsilyl bromide (0.424 mL, 3.21 mmol). The clear solution is stirred at room temperature for 18 hours, then concentrated in vacuo. The residue is triturated with water (5 mL) and the precipitate is filtered off and then dissolved in 1N sodium hydroxide (5 mL). 1N Hydrochloric acid (8 mL) is added to precipitate the product which is filtered and washed with water (10 mL). The solid suspended in ethanol (5 mL) and stirred for 20 minutes with propylene oxide (2 mL). Concentration in vacuo yields (S)-5-(biphenyl-4-yl)-4-(phosphonomethylamino)-2-pentenoic acid as a white solid; m.p.: 231°-233°.

Workup

  1. extractionThe carboxylic acid is extracted in methylene chloride (20 mL)
  2. customThe organic layer is separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringThe clear solution is stirred at room temperature for 18 hours
  7. concentrationconcentrated in vacuo
  8. customThe residue is triturated with water (5 mL)
  9. filtrationthe precipitate is filtered off
  10. dissolutiondissolved in 1N sodium hydroxide (5 mL)
  11. addition1N Hydrochloric acid (8 mL) is added
  12. customto precipitate the product which
  13. filtrationis filtered
  14. washwashed with water (10 mL)
  15. stirringstirred for 20 minutes with propylene oxide (2 mL)
  16. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-047e9f2eb44d45ff903ae4afcdad492a
Source dataset
uspto-grants-1993_10
Patent number
US05250522

Reaction notes

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