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

HRID 747539Notes

Reaction equation

HRID 747539 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(OCC)(=O)C>O>[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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 10340Sodium Carbonate2×HCID 589060822-Hydroxy-4-(hydroxyimino)-2-[(1H-indol-3-yl)methyl]pentanedioic acid

Product 1

HCID 58650636(4S)-4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acidYield 72.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

44.7 g (0.131 mol) of the ammonium salt of 4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid was dissolved in 500 ml of water at 25° C. The resulting aqueous solution was adjusted to pH 2, using 25.5 g of 36% hydrochloric acid. The acidic solution was extracted in 1300 ml of ethyl acetate. The ethyl acetate solution was rinsed with 200 ml of aqueous saturated sodium chloride. 500 ml of aqueous sodium carbonate solution (13.9 g (0.131 mol) of sodium carbonate) was added to the resulting ethyl acetate solution, for agitation to separate the aqueous alkaline solution from ethyl acetate. 23.1 g of 36% hydrochloric acid was added to the resulting aqueous alkaline solution to adjust the solution to pH 2. (R)-(+)-1-phenylethylamine of 6.99 g (57.6 mmol) is dropwise added to the resulting acidic solution, for agitation at 25° C. for one hour. The resulting crystal was filtered and dried under reduced pressure, to obtain the (R)-(+)-1-phenylethylaine salt (21.8 g; 47.8 mmol) of (4S)-4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid (at a yield of 72.7% and optical purity of 87.4%).

Workup

  1. extractionThe acidic solution was extracted in 1300 ml of ethyl acetate
  2. washThe ethyl acetate solution was rinsed with 200 ml of aqueous saturated sodium chloride
  3. customto separate the aqueous alkaline solution from ethyl acetate
  4. addition23.1 g of 36% hydrochloric acid was added to the resulting aqueous alkaline solution
  5. addition(R)-(+)-1-phenylethylamine of 6.99 g (57.6 mmol) is dropwise added to the resulting acidic solution, for agitation at 25° C. for one hour
  6. filtrationThe resulting crystal was filtered
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-6888957c62ed493d9229f87370ce53d2
Source dataset
uspto-grants-2008_07
Patent number
US07396941B2

Reaction notes

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