Ethyl 4,6-dichloro-4-fluoro-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate → 3-(2-Carboxyethyl)-4,6-dichloro-4-fluoro-1H-indole-2-carboxylic acid

HRID 1950681Notes

Reaction equation

HRID 1950681 reaction equation
[Cl:1][C:2]1([F:24])[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]1=[C:4]([CH2:17][CH2:18][C:19]([O:21]CC)=[O:20])[CH:5]([C:12]([O:14]CC)=[O:13])[NH:6]2.O.O.O.[OH-].[Li+]>O1CCCC1.O>[C:19]([CH2:18][CH2:17][C:4]1[CH:5]([C:12]([OH:14])=[O:13])[NH:6][C:7]2[C:3]=1[C:2]([Cl:1])([F:24])[CH:10]=[C:9]([Cl:11])[CH:8]=2)([OH:21])=[O:20]

Participants

5

Reactant 2

HCID 71280672Ethyl 4,6-dichloro-4-fluoro-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylateHCID 86677587Lithium hydroxide trihydrate

Product 1

HCID 712808413-(2-Carboxyethyl)-4,6-dichloro-4-fluoro-1H-indole-2-carboxylic acidYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 4,6-dichloro-4-fluoro-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate (1.13 g, 3 mmol) was dissolved in 15 ml tetrahydrofurane (THF) with stirring at rt. Then a solution of 0.38 g of lithium hydroxide trihydrate (3 equiv.) in 15 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 (3×15 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. 292-294° C. 1H-NMR (DMSO-d6) δ 2.48 (m, 2H, 2′-H); 3.48 (m, 2H, 1′-H); 7.49 (dd, 1H, 2J=6 Hz, 7-H); 11.98 (s, 1H, NH); 12.72 (b, 2H, 2CO2H). 13C-NMR (DMSO-d6) δ 20.1 (C-2′); 36.1 (C-1′); 112.5 (C-7); 113.0, 113.2, 117.6, 117.7, 121.3, 121.4 (C-5); 122.3 (C-4); 127.7 (C-6); 132.5 (C-3); 147.2 (C-3a); 149.0 (C-2); 162.5 (2′-CO2H), 173.6 (2-CO2H). LC-MS (m/z): 337 [M-NH4+]+, 320 [M]+, 318 [M]−. Purity (LC-MS): 98.6%.

Workup

  1. stirringto stir at rt for 24 h
  2. customwas removed under reduced pressure
  3. extractionthe product was extracted with diethyl ether (3×15 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-0cc34827bfd54f0da5ace0a79e3f339a
Source dataset
uspto-grants-2013_03
Patent number
US08404436B1

Reaction notes

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