N-Acetyl-L-Cysteine → (1RS,4SR,5SR,6RS)ethyl 6-fluoro-4-hydroxy-2-oxobicyclo[3.1.0]hexane-6-carboxylate

HRID 2271285

Reaction equation

HRID 2271285 reaction equation
[C:1](N[C@H](C(O)=O)CS)(=O)[CH3:2].O.O.O.O.O.O.O.O.O.O.B([O-])([O-])[O-].B([O-])([O-])[O-].B([O-])([O-])[O-].B([O-])([O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].C1([SeH-](C2C=CC=CC=2)=[Se])C=CC=CC=1.[O:63]1[CH:69]2[CH:64]1[C:65](=[O:74])[CH:66]1[CH:68]2[C:67]1([F:73])[C:70]([O-:72])=[O:71]>O.C(O)C.O.O1CCCC1>[F:73][C:67]1([C:70]([O:72][CH2:1][CH3:2])=[O:71])[CH:66]2[CH:68]1[CH:69]([OH:63])[CH2:64][C:65]2=[O:74]

Participants

8

Reactant 4

HCID 12035N-Acetyl-L-CysteineHCID 86618040Sodium tetraborate decahydrate; Solubor; Solubor DF; Three Elephant; TincalHCID 867576963,4-Epoxy-6-fluoro-2-oxobicyclo [3.1.0]hexane-6-carboxylateHCID 178528034HCID 178528034, compound

Product 1

HCID 69853523(1RS,4SR,5SR,6RS)ethyl 6-fluoro-4-hydroxy-2-oxobicyclo[3.1.0]hexane-6-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
38 °C

Procedure

Under a nitrogen atmosphere, 23.2 g of N-acetyl-L-cystein, 54.3 g of sodium tetraborate decahydrate and 0.7 g of diphenyldiselenide were suspended in 450 ml of a water-ethanol (1:1) mixture solution which had been deaerated. 9.5 g of (1RS,3RS,4RS,5SR,6RS)ethyl (3,4-epoxy-6-fluoro-2-oxobicyclo [3.1.0]hexane-6-carboxylate dissolved into 225 ml of tetrahydrofuran was added thereto, and this was stirred at room temperature for one day, at 38° C. for 12 hours, and at 85° C. for 5 hours. After the reaction solution was cooled down to room temperature, it was poured into water and extracted three times with diethyl ether. The obtained organic layers were consolidated and dried over anhydrous sodium sulfate. After filtering off the desiccant, concentration of the filtrate was carried out under reduced pressure. The residue was purified by column chromatography (silica gel: Wako gel (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=3:1 to 1:1), yielding 3.9 g of (1RS,4SR,5SR,6RS)ethyl 6-fluoro-4-hydroxy-2-oxobicyclo[3.1.0]hexane-6-carboxylate. The proton NMR and mass spectrograph data are shown below.

Workup

  1. additionwas added
  2. waitat 85° C. for 5 hours
  3. temperatureAfter the reaction solution was cooled down to room temperature
  4. extractionextracted three times with diethyl ether
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtering off the desiccant, concentration of the filtrate
  7. customThe residue was purified by column chromatography (silica gel: Wako gel (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=3:1 to 1:1)

Sources & evidence

ORD record
ord-9330732d1e6a40969f6c8e9d04239b4e
Source dataset
uspto-grants-2001_12
Patent number
US06333428B1

Linked notes

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