D-Tartaric acid → 2,3-Dihydroxybutanedioic Acid

HRID 1670633Notes

Reaction equation

HRID 1670633 reaction equation
C(OC(N1CCC(NCC2C=CC=CC=2)C(O)C1)=O)(C)(C)C.[C:23]([OH:32])(=[O:31])[C@H:24]([C@@H:26]([C:28]([OH:30])=[O:29])[OH:27])[OH:25]>C(#N)C.O>[C:23]([OH:32])(=[O:31])[CH:24]([CH:26]([C:28]([OH:30])=[O:29])[OH:27])[OH:25]

Participants

4

Reactant 2

HCID 439655D-Tartaric acidHCID 57452747Tert-butyl-4-(benzylamino)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 8752,3-Dihydroxybutanedioic Acid

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Concentrate the mother liquor of Preparation 77 to obtain enantio enriched (3S,4S)-3-hydroxy-4-phenethyl-piperidine-1-carboxylic acid tert-butyl ester L-(+)-tartaric acid salt (0.0377 mol, 17.2 g). Add 4% aqueous potassium carbonate solution (500 mL) and stir for 30 min. Extract the free amine with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to obtain the free amine (11.0 g). Heat a mixture of 4-benzylamino-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.0361 mol, 11.0 g) and D-(−)-tartaric acid (0.0397 mol, 5.97 g, 1.1 equiv.) in acetonitrile/water (20:1) (100 ml) at 75° C. for 4 h. Concentrate the reaction mixture under reduce pressure to obtain crude tartaric acid salt. Crystallize the residue from acetonitrile three times. Filter the crystals and dry under vacuum to obtain the title compound (14.8 g, 90%). HPLC (Column: Chiralcel OD-H (250 mm*4.6 mm); solvent system: isopropanol/0.1% triethylamine in hexanes (8:92); flow rate: 0.800 ml/min; wavelength: 258 nm): 96.4% ee. tR 8.714 min. tR for opposite enantiomer ((3R,4R)-3-Hydroxy-4-phenethyl-piperidine-1-carboxylic acid tert-butyl ester.L-(+)-tartaric acid salt) 9.502 min.

Workup

  1. temperatureHeat
  2. concentrationConcentrate the reaction mixture

Sources & evidence

ORD record
ord-e181379ba33748cb9fa987abfb1e0483
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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