Acetic Acid → 1-(4-(3-(4-tert-Butylphenyl)-2-oxoimidazolidin-1-yl)benzyl)azetidine-3-carboxylic acid

HRID 1710336Notes

Reaction equation

HRID 1710336 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH2:14][N:13]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=3)[C:12]2=[O:24])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[NH:29]1[CH2:32][CH:31]([C:33]([OH:35])=[O:34])[CH2:30]1.C([BH3-])#N.[Na+]>ClCCl.CO.CS(C)=O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:15][CH2:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]([CH2:20][N:29]4[CH2:32][CH:31]([C:33]([OH:35])=[O:34])[CH2:30]4)=[CH:22][CH:23]=3)[C:12]2=[O:24])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 594568184-(3-(4-tert-Butylphenyl)-2-oxoimidazolidin-1-yl)benzaldehyde

Product 1

HCID 247719691-(4-(3-(4-tert-Butylphenyl)-2-oxoimidazolidin-1-yl)benzyl)azetidine-3-carboxylic acidYield 10%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 4-(3-(4-tert-butylphenyl)-2-oxoimidazolidin-1-yl)benzaldehyde (32 mg, 0.1 mmol), acetic acid (50 μl) and azetidine-3-carboxylic acid (13 mg, 0.13 mmol) in dichloromethane/MeOH (1:1, 5 mL) was stirred at room temperature for 1 hour. Sodium cyanoborohydride (3.5 mg, 0.05 mmol) was added and the reaction mixture was stirred for 6 hour at room temperature. After concentration of solvent under reduced pressure, the resulting residue was dissolved in dimethylsulfoxide, filtered and purified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5u C18(2) column, 60×21.2 mm ID, mobile phase: A=0.05% TFA in water; B=0.05% TFA in acetonitrile. The flow rate was 10-12 mL/min) to yield the title product 4 mg (10%): 1H NMR (400 MHz, CDOD3) δ 7.72 (d, 2H), 7.51-7.40 (m, 6H), 4.33 (s, 2H), 4.28 (m, 4H), 4.02 (s, 4H), 3.64 (m, 1H), 1.32 (s, 9H). MS (ESI) m/z: Calculated: 407.22; Observed: 408.00 (M++1).

Workup

  1. stirringthe reaction mixture was stirred for 6 hour at room temperature
  2. filtrationfiltered
  3. custompurified by reverse phase preparative HPLC (Phenomenex

Sources & evidence

ORD record
ord-a26a6cb982be419891de9650f07f65f0
Source dataset
uspto-grants-2010_09
Patent number
US07790707B2

Reaction notes

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