Chloroacetic Acid → 4-(3-{1-Benzhydryl-5-chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-propyl)-benzoic acid ethyl ester

HRID 1392598Notes

Reaction equation

HRID 1392598 reaction equation
[CH:1]([N:14]1[C:22]2[C:17](=[CH:18][C:19]([Cl:23])=[CH:20][CH:21]=2)[CH:16]=[C:15]1[CH2:24][CH2:25][N:26]1[C:34](=[O:35])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]1=[O:36])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.[CH2:44]([O:46][C:47](=[O:58])[C:48]1[CH:53]=[CH:52][C:51]([CH2:54][CH2:55][CH:56]=O)=[CH:50][CH:49]=1)[CH3:45].ClCC(O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.CO.O>[CH2:44]([O:46][C:47](=[O:58])[C:48]1[CH:53]=[CH:52][C:51]([CH2:54][CH2:55][CH2:56][C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=3)[N:14]([CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:15]=2[CH2:24][CH2:25][N:26]2[C:27](=[O:36])[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:34]2=[O:35])=[CH:50][CH:49]=1)[CH3:45]

Participants

9

Reactant 5

HCID 300Chloroacetic AcidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 2757377Ethyl 4-(3-oxopropyl)benzoateHCID 112488722-[2-(1-Benzhydryl-5-chloro-1H-indol-2-yl)-ethyl]-isoindole-1,3-dione

Product 1

HCID 113199214-(3-{1-Benzhydryl-5-chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-propyl)-benzoic acid ethyl esterYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4.91 g (10.0 mmol, 1 eq) 2-[2-(1-Benzhydryl-5-chloro-1H-indol-2-yl)-ethyl]-isoindole-1,3-dione made according to Example 3 was suspended in 50 mL CH2Cl2. 3.50 g (30.0 mmol, 3 eq) triethylsilane, 2.47 g (12 mmol, 1.2 eq) 4-(3-Oxo-propyl)-benzoic acid ethyl ester and chloro-acetic acid 7.56 g (80 mmol, 8 eq) were added in one portion. The mixture was heated to reflux for 92 h. LC showed less then 2% starting material at this end point. 15 mL sat. aq. NaHCO3 and 10 mL water was added to the reaction mixture, and stirring was continued over a period of 16 h. 10 mL MeOH was then added and the solid was collected by filtration. 9.4 g off-white solid was dried in the oven for 3 h at 60° C. to give 6.12 g 4-(3-{1-Benzhydryl-5-chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-propyl)-benzoic acid ethyl ester (90% yield) with 74% purity.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 92 h
  3. filtrationthe solid was collected by filtration
  4. dry with material9.4 g off-white solid was dried in the oven for 3 h at 60° C.

Sources & evidence

ORD record
ord-384d1fd285fd4bd58c5f4ac8844360c0
Source dataset
uspto-grants-2008_03
Patent number
US07342119B2

Reaction notes

Loading…