Hydrochloric Acid → (4S)-4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid

HRID 2222059Notes

Reaction equation

HRID 2222059 reaction equation
[OH:1][C:2]([CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)([C:10]([OH:12])=[O:11])[CH2:3][C:4](=[N:8][OH:9])[C:5]([OH:7])=[O:6].Cl.C(=O)([O-])[O-].[Na+].[Na+].[C:30]1([C@H:36]([NH2:38])[CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O.C(OCC)(=O)C>[C:30]1([C@H:36]([NH2:38])[CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH:1][C@:2]([CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)([C:10]([OH:12])=[O:11])[CH2:3][C:4](=[N:8][OH:9])[C:5]([OH:7])=[O:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 6431891-Phenethylamine, (+)-HCID 589060822-Hydroxy-4-(hydroxyimino)-2-[(1H-indol-3-yl)methyl]pentanedioic acid

Product 2

HCID 6431891-Phenethylamine, (+)-HCID 58650636(4S)-4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acidYield 72.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ammonium salt (44.7 g, 0.131 mol) of 4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid was dissolved in 500 mL of water at 25° C., and subsequently the pH value of the aqueous solution was adjusted to 2 with 25.5 g of 36% hydrochloric acid. The acidic solution was subject to extraction with 1300 mL of ethyl acetate, and the ethyl acetate solution was washed with 200 mL of saturated aqueous NaCl solution. An aqueous solution (500 mL) of sodium carbonate (13.9 g, 0.131 mol) was added to the resulting ethyl acetate solution, and stirred to separate an alkali aqueous solution from ethyl acetate. The pH value of the resulting alkali aqueous solution was adjusted to 2 by adding 23.1 g of 36% hydrochloric acid. (R)-(+)-1-Phenylethylamine (6.99 g, 57.6 mmol) was dripped into the resulting acidic aqueous solution, and stirred at 25° C. for one hour. The yielded crystal was filtered, and dried under reduced pressure to yield 21.8 g (47.8 mmol) of (R)-(+)-1-phenylethylamine salt of (4S)-4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid (yield: 72.7%, optical purity: 87.4%).

Workup

  1. extractionThe acidic solution was subject to extraction with 1300 mL of ethyl acetate
  2. washthe ethyl acetate solution was washed with 200 mL of saturated aqueous NaCl solution
  3. customto separate an alkali aqueous solution from ethyl acetate
  4. additionby adding 23.1 g of 36% hydrochloric acid
  5. stirringstirred at 25° C. for one hour
  6. filtrationThe yielded crystal was filtered
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-dbbcc4afdade4f94b16b818bbf674b7a
Source dataset
uspto-grants-2008_05
Patent number
US07371549B2

Reaction notes

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