Hydrochloric Acid → (S)-N-(2-nitrobenzenesulfonyl )azetidine-2-carboxylic acid

HRID 1058202Notes

Reaction equation

HRID 1058202 reaction equation
C(OC([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12]([OH:14])=[O:13])=O)(C)(C)C.S(=O)(=O)(O)O.Cl.C(=O)([O-])[O-].[Na+].[Na+].[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36](Cl)(=[O:38])=[O:37])([O-:29])=[O:28]>O.O1CCCC1>[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12]([OH:14])=[O:13])(=[O:38])=[O:37])([O-:29])=[O:28]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 10340Sodium Carbonate2×HCID 155402-Nitrobenzenesulfonyl chlorideHCID 2734495(2S)-1-((tert-butoxy)carbonyl)azetidine-2-carboxylic acid

Product 1

HCID 11033444(S)-N-(2-nitrobenzenesulfonyl )azetidine-2-carboxylic acidYield 89.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixed solution of tetrahydrofuran (70 ml)/water (60 ml) containing (S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (20.51 g; also containing (R)-isomer) and sulfuric acid (10.03 g) was stirred for 1 hour under ice cooling, 1.5 hours at room temperature, and for 28 hours under heating at 45 to 48° C. On the way, 6 N hydrochloric acid (20 ml) was further added after about 20 hours. The reaction mixture was cooled with ice, and sodium carbonate (38.92 g), 2-nitrobenzenesulfonyl chloride (29.42 g), tetrahydrofuran (50 ml) and water (60 ml) were added in turn thereto, followed by stirring for 70 minutes under ice cooling and for 37 hours at room temperature. On the way, sodium carbonate (5.45 g) was further added after 30 minutes. Water (140 ml) was added to the reaction mixture, and the organic solvent was removed by evaporation under reduced pressure. Then, water (40 ml) and ethyl acetate (140 ml) were added, followed by extraction and solution separation, and the organic layer was extracted again with water (100 ml). Ethyl acetate (30 ml) and concentrated hydrochloric acid (40 ml) were added to the resulting aqueous layer, and ethyl acetate (100 ml) was further added, followed by extraction and solution separation. The aqueous layer was extracted again with ethyl acetate (120 ml). The resulting organic layer was dried over sodium sulfate, filtered, concentrated and dried under vacuum to obtain (S)-N-(2-nitrobenzenesulfonyl)azetidine-2-carboxylic acid (26.2 g; yield: 89.8%). Analysis according to high performance liquid chromatography (HPLC) resulted in 46.4% ee.

Workup

  1. temperaturefor 28 hours under heating at 45 to 48° C
  2. additionwere added in turn
  3. stirringby stirring for 70 minutes under ice cooling and for 37 hours at room temperature
  4. customthe organic solvent was removed by evaporation under reduced pressure
  5. additionThen, water (40 ml) and ethyl acetate (140 ml) were added
  6. extractionfollowed by extraction and solution separation
  7. extractionthe organic layer was extracted again with water (100 ml)
  8. additionEthyl acetate (30 ml) and concentrated hydrochloric acid (40 ml) were added to the resulting aqueous layer, and ethyl acetate (100 ml)
  9. additionwas further added
  10. extractionfollowed by extraction and solution separation
  11. extractionThe aqueous layer was extracted again with ethyl acetate (120 ml)
  12. dry with materialThe resulting organic layer was dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customdried under vacuum

Sources & evidence

ORD record
ord-4a01bfad72d441a5b64c36dc06e3043b
Source dataset
uspto-grants-2003_02
Patent number
US06515179B2

Reaction notes

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