1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67377609, compound

HRID 2190593Notes

Reaction equation

HRID 2190593 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[I:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[CH3:31])[NH2:27].CCN=C=NCCCN(C)C>C(Cl)Cl>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:21])[NH:27][C:26]3[CH:28]=[CH:29][C:30]([CH3:31])=[C:24]([I:23])[CH:25]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:2])([CH3:6])([CH3:5])[CH3:7]

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 1188893-Iodo-p-toluidineHCID 224928594-(4-Carboxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67377609HCID 67377609, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-Boc-4-(4-carboxyphenyl)piperidine (200 mg, 0.66 mmol) and 3-iodo-4-methyl aniline (153 mg, 0.72 mmol) in DCM (10 mL) was treated with EDCI (380 mg, 1.98 mmol) at rt. After stirring for 48 hr at rt the reaction mixture was partitioned between EtOAc and water. The EtOAc layer was collected, concentrated and the residue was chromatographed on a silica gel column with a 0-30% EtOAc in hexanes to afford the corresponding intermediate 4-[4-(3-Iodo-4-methyl-phenylcarbamoyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester. This intermediate was then dissolved in a 30% TFA in CH2Cl2 mixture (10 mL). Upon consumption of the starting material, as judged by TLC, the solution was partitioned between EtOAc and water. The water layer was basified to pH 12 with solid NaOH. The organic layer was then collected, dried over Na2SO4, filtered and concentrated to a residue that without further delay was dissolved in DMSO (5 mL). The mixture was then treated with 4-fluoro ethyl benzoate (550 mg, 3.28 mmol), diisopropyl ethyl amine (3 mL) and a catalytic amount of DMAP and heated at 120° C. in a sealed tube for 4 days. The reaction mixture was then cooled, partitioned between EtOAc and water. The EtOAc layer was collected dried over Na2SO4 filtered and concentrated to a solid that after suspension in CH2Cl2 and filtration afforded the product (100 mg, Yield: 53%). HRMS m/z calcd for C28H29N2O3I [M+H]+: 569.1296. Found: 569.1294.

Workup

  1. customwas partitioned between EtOAc and water
  2. customThe EtOAc layer was collected
  3. concentrationconcentrated
  4. customthe residue was chromatographed on a silica gel column with a 0-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-baf93ffea33849468eb6958440e6cf16
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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