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

HRID 730944Notes

Reaction equation

HRID 730944 reaction equation
[CH2:1]([O:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:2].C([SiH]([CH2:17][CH3:18])CC)C.[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]([CH2:29][CH2:30][N:31]1[C:39](=[O:40])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]1=[O:41])=[CH:23]2.F[C:43](F)(F)C(O)=O>ClCCl.CO.C(N(CC)CC)C>[CH2:1]([O:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][C:8]([CH2:43][CH2:17][CH2:18][C:23]2[C:22]3[C:26](=[CH:27][CH:28]=[C:20]([Cl:19])[CH:21]=3)[NH:25][C:24]=2[CH2:29][CH2:30][N:31]2[C:32](=[O:41])[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:39]2=[O:40])=[CH:7][CH:6]=1)[CH3:2]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7165Ethyl benzoateHCID 12052TriethylsilaneHCID 534240202-[2-(5-Chloro-1H-indol-2-YL)-ethyl]-isoindole-1,3-dione

Product 1

HCID 117204684-(3-{5-Chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-propyl)-benzoic Acid Ethyl EsterYield 50%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
5 °C

Procedure

To a solution 4-(3-oxo-propyl)-)-benzoic acid ethyl ester (381 g, 1.85 mol), triethylsilane ((537 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 (4 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 (778 g) and methanol (3 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 (313 g) in 50% yield. 1H NMR (CDCl3): δ6.9-8.2 (m, Ph, CHPh2), 4.35 (dd, 2H, J=14.3 Hz, 7.2 Hz), 3.99 (t, 2H, J=7.1 Hz), 3.13 (t, 2H, J=7.2 Hz), 2.69 (t, 4H, J=7.3 Hz) 1.90 (m, 2H), 1.38 (t, 3H, J=7.1 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-8985b32e071243ee837e942505faea33
Source dataset
uspto-grants-2009_09
Patent number
US07582771B2

Reaction notes

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