Acetic Acid → 1-{5-[1-(4-Chloro-3-methyl-phenyl)-propylamino]-2-methyl-benzyl}-azetidine-3-carboxylic acid

HRID 1629706Notes

Reaction equation

HRID 1629706 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([CH3:20])=[C:16]([CH:19]=2)[CH:17]=O)[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:21].[NH:22]1[CH2:25][CH:24]([C:26]([OH:28])=[O:27])[CH2:23]1.CC(O)=O.[BH3-]C#N.[Na+]>CO.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([CH3:20])=[C:16]([CH:19]=2)[CH2:17][N:22]2[CH2:25][CH:24]([C:26]([OH:28])=[O:27])[CH2:23]2)[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:21]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 575173205-[1-(4-Chloro-3-methyl-phenyl)-propylamino]-2-methyl-benzaldehyde

Product 1

HCID 533403201-{5-[1-(4-Chloro-3-methyl-phenyl)-propylamino]-2-methyl-benzyl}-azetidine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of INT 9 (200 mg, 0.66 mmol) and azetidine-3-carboxylic acid (67 mg, 0.66 mmol) in MeOH (6.5 mL) was added HOAc (0.038 mL, 0.66 mmol) followed by NaCNBH3 (42 mg, 0.66 mmol). The reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with saturated aqueous NaHCO3 and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by preparative HPLC (H2O/CH3CN) to afford the title compound Example 4.

Workup

  1. extractionextracted with CH2Cl2 (2×)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC (H2O/CH3CN)

Sources & evidence

ORD record
ord-2e74b885148c4478b1b2e7df4e931475
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

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