Hydrochloric Acid → (S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid

HRID 389863Notes

Reaction equation

HRID 389863 reaction equation
[NH:1]1[CH2:4][CH2:3][C@H:2]1[C:5]([OH:7])=[O:6].Cl.Br[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1>[Cu](I)I.CC(N(C)C)=O>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([N:1]2[CH2:4][CH2:3][C@H:2]2[C:5]([OH:7])=[O:6])=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 7806p-BromochlorobenzeneHCID 16486L-Azetidine-2-carboxylic acid

Product 1

HCID 67284015(S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube is charged with (S)-Azetidine-2-carboxylic acid; hydrochloride (2 g; 19.8 mmol), 4-bromochlorobenzene (3.8 g; 19.8 mmol) and copper iodide (I) (0.38 g; 1.99 mmol) is evacuated and back-filled with Argon 3 times. Dimethylacetamide (40 mL) is added and the tube is sealed and purged with Argon and evacuated 3 times. The sealed tube is heated in 110° C. oil bath for 72 hours. After this time, the reaction mixture is cooled to room temperature and partitioned between ethyl acetate and water. The organic layer is discarded. The aqueous layer is acidified to PH˜1 by adding 1N hydrochloric acid and then extracted with ethyl acetate twice. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using methanol/methylene chloride provides the title compound, m/z 212 [M+H+].

Workup

  1. additionback-filled with Argon 3 times
  2. customthe tube is sealed
  3. custompurged with Argon
  4. customevacuated 3 times
  5. temperatureAfter this time, the reaction mixture is cooled to room temperature
  6. custompartitioned between ethyl acetate and water
  7. additionby adding 1N hydrochloric acid
  8. extractionextracted with ethyl acetate twice
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-6afbc2057c354a3cbee3a4cf940605c2
Source dataset
uspto-grants-2013_02
Patent number
US08383615B2

Reaction notes

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