Ethyl 4,6-diphenyl-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate → 3-(2-carboxyethyl)-4,6-diphenyl-1H-indole-2-carboxylic acid

HRID 1950683Notes

Reaction equation

HRID 1950683 reaction equation
[C:1]1([C:7]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:13]=[C:12]3[C:8]=2[C:9]([CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[C:10]([C:22]([O:24]CC)=[O:23])[NH:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.O.O.[OH-].[Li+]>O1CCCC1.O>[C:29]([CH2:28][CH2:27][C:9]1[C:8]2[C:12](=[CH:13][C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:15][C:7]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[NH:11][C:10]=1[C:22]([OH:24])=[O:23])([OH:31])=[O:30]

Participants

5

Reactant 2

HCID 71281244Ethyl 4,6-diphenyl-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylateHCID 86677587Lithium hydroxide trihydrate

Product 1

HCID 712811613-(2-carboxyethyl)-4,6-diphenyl-1H-indole-2-carboxylic acidYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 4,6-diphenyl-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate (4.42 g, 10 mmol) was dissolved in 25 ml tetrahydrofurane (THF) with stirring at rt. Then a solution of 1.26 g of lithium hydroxide trihydrate (3 equiv.) in 25 ml water was added and the resulting mixture was let to stir at rt for 24 h. After completion of the reaction THF was removed under reduced pressure and the pH was adjusted to 4-5, and the product was extracted with diethyl ether (3×25 ml). The organic layers were dried over magnesium sulfate, filtered, and evaporated to dryness to yield a light-beige-colored solid in 95-100% yield. mp. 243-245° C. 1H-NMR (DMSO-d6) δ 2.07 (m, 2H, 2′-H); 2.83 (m, 2H, 1′-H); 7.09 (d, 1H, 2J=1.6 Hz, 7-H); 7.34 (t, 1H, 3J=7.4 Hz, ph-ring), 7.44 (m, 7H, Ph-ring), 7.66 (d, 2H, 2J=0.9 Hz, 5-H); 7.68 (d, 1H, 1.6 Hz, Ph-ring); 11.72 (s, 1H, NH); 12.33 (b, 2H, 2CO2H). 13C-NMR (DMSO-d6) δ 20.3 (C-2′); 34.9 (C-1′); 109.5 (C-4); 120.9 (C-6); 121.7 (C-3); 123.8 (C-2); 125.5 (C-3a); 127.0 (C-2″, C-6″); 127.3 (C-4″′); 127.5 (C-4″); 128.0 (C-3′″, C-5″′); 129.0 (C-3″, C-5″); 129.1 (C-2′″, C-6″′); 135.4 (C-7a); 137.3 (C-4), 137.4 (C-6); 140.8 (C-1″); 141.0 (C-1′″); 163.1 (2′-CO2H); 173.4 (2-CO2H). LC-MS (m/z): 386 [M-NH4+]+, 366 [M]+, 384 [M]−. Purity (LC-MS): 95%.

Workup

  1. stirringto stir at rt for 24 h
  2. customwas removed under reduced pressure
  3. extractionthe product was extracted with diethyl ether (3×25 ml)
  4. dry with materialThe organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customto yield a light-beige-colored solid in 95-100% yield

Sources & evidence

ORD record
ord-2a23914cd36847878372c0bd0f8fd2b8
Source dataset
uspto-grants-2013_03
Patent number
US08404436B1

Reaction notes

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