Trifluoroacetic acid → 4-(2-{5-Chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic Acid Methyl Ester

HRID 730943Notes

Reaction equation

HRID 730943 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:12](OCC)OCC)=[CH:6][CH:5]=1.C([SiH](CC)CC)C.[Cl:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32]([CH2:37][CH2:38][N:39]1[C:47](=[O:48])[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]1=[O:49])=[CH:31]2.FC(F)(F)C(O)=O>ClCCl.CO.C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH2:12][C:31]2[C:30]3[C:34](=[CH:35][CH:36]=[C:28]([Cl:27])[CH:29]=3)[NH:33][C:32]=2[CH2:37][CH2:38][N:39]2[C:40](=[O:49])[C:41]3[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:47]2=[O:48])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 10084384Methyl 4-(2,2-diethoxyethoxy)benzoateHCID 534240202-[2-(5-Chloro-1H-indol-2-YL)-ethyl]-isoindole-1,3-dione

Product 1

HCID 690536944-(2-{5-Chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic Acid Methyl EsterYield 62.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
5 °C

Procedure

To a solution 4-(2,2-diethoxy-ethoxy)-benzoic acid methyl ester (495 g, 1.84 mol), triethylsilane ((536 g, 4.62 mol) and 2-[2-(5-chloro-1 H-indol-2-yl)-ethyl]-isoindole-1,3-dione (500 g, 1.54 mol) in dichloromethane (3.5 L) was added trifloroacetic acid (878 g, 7.7 mol) during a period of 1 hour. Then, the reaction mixture was cooled to 0-10° C. A mixture of triethyl amine (787 g) and methanol (4 L) was added during a period of 45 min. The reaction mixture was stirred for 1 h at 0-10° C. and filtered. The crude product was washed with methanol (2×1000 mL) and dried to give a white solid (483 g) in 62% yields and 88.1% area purity. 1H NMR (CDCl3): δ6.9-8.6 (m, Ph, CHPh2), 4.13 (t, 2H, J=6.6 Hz), 4.04 (t, 2H, J=7.2 Hz), 4.13 (t, 2H, J=6.6 Hz), 3.87 (S, 3H), 3.23 (t, 2H, J=7.2 Hz), 3.16 (t, 2H, J=6.6 Hz).

Workup

  1. additionwas added during a period of 45 min
  2. filtrationfiltered
  3. washThe crude product was washed with methanol (2×1000 mL)
  4. customdried

Sources & evidence

ORD record
ord-44aafd1c147647dabe625fd6800d013b
Source dataset
uspto-grants-2009_09
Patent number
US07582771B2

Reaction notes

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