Hydrochloric Acid → 1-{2-Chloro-5-[(R)-1-(4-chloro-3,5-dimethyl-phenyl)-propylamino]-benzyl}-azetidine-3-carboxylic acid

HRID 1629749Notes

Reaction equation

HRID 1629749 reaction equation
C([O:5][C:6]([CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:18]=[C:17]([NH:19][C@@H:20]([C:23]3[CH:28]=[C:27]([CH3:29])[C:26]([Cl:30])=[C:25]([CH3:31])[CH:24]=3)[CH2:21][CH3:22])[CH:16]=[CH:15][C:14]=2[Cl:32])[CH2:9]1)=[O:7])(C)(C)C.Cl>C(Cl)Cl>[Cl:32][C:14]1[CH:15]=[CH:16][C:17]([NH:19][C@@H:20]([C:23]2[CH:28]=[C:27]([CH3:29])[C:26]([Cl:30])=[C:25]([CH3:31])[CH:24]=2)[CH2:21][CH3:22])=[CH:18][C:13]=1[CH2:12][N:10]1[CH2:9][CH:8]([C:6]([OH:7])=[O:5])[CH2:11]1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 673461981-{2-Chloro-5-[(R)-1-(4-chloro-3,5-dimethyl-phenyl)-propylamino]-benzyl}-azetidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 533395461-{2-Chloro-5-[(R)-1-(4-chloro-3,5-dimethyl-phenyl)-propylamino]-benzyl}-azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of INT 58 (206 mg, 0.431 mmol) in CH2Cl2 (5 mL) was treated with HCl (4 M in dioxane, 0.43 mL, 1.726 mmol) and stirred at room temperature overnight. The mixture contained some starting material, so another portion of HCl (4 M in dioxane, 0.50 ml, 2.00 mmol) was added and stirring continued for 4 hours. Excess of HCl gas was removed by a stream of argon. The mixture was neutralized with 10% sodium bicarbonate solution then treated with 10% ammonium chloride solution and extracted first with CH2Cl2 then with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The title compound was purified by preparative UPLC (H2O/CH3CN).

Workup

  1. stirringstirring
  2. waitcontinued for 4 hours
  3. customExcess of HCl gas was removed by a stream of argon
  4. additionthen treated with 10% ammonium chloride solution
  5. extractionextracted first with CH2Cl2
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe title compound was purified by preparative UPLC (H2O/CH3CN)

Sources & evidence

ORD record
ord-b4d472d77a394a3093326a0ebdecb420
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

Loading…