Réaction #70810

Équation de réaction

aluminum

lithium hydroxide

H2O

methyl 6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylate

→

6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylic acid

Rendement 76.2%

Solvants

Tetrahydrofuran

Methanol

Conditions de réaction

Traitement

1. 1
   AutreReaction progress
2. 2
   AutreLCMS (18 h)
3. 3
   workup.STIRRINGwith stirring
4. 4
   AutreAfter complete conversion the solvent was removed in-vacuo
5. 5
   workup.DISSOLUTIONthe remaining residue was dissolved with water (1 ml) and 1N HCl
6. 6
   workup.ADDITIONwas added dropwise (9 drops)
7. 7
   Autreuntil precipitation
8. 8
   FiltrationThe fine pale-yellow solid was collected by vacuum filtration

Mode opératoire

To a 100 ml round bottom flask was added methyl 6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylate (33.0 mg, 0.105 mmol), Methanol (700 μl), Tetrahydrofuran (THF) (1401 μl) and a magnetic stir bar. To the same was added lithium hydroxide, H2O (13.22 mg, 0.315 mmol) and the mixture was stirred at room temperature. Reaction progress was monitored by LCMS. LCMS (18 h) showed 60% conversion. The reaction was heated to 50° C. in an aluminum heating block with stirring. After complete conversion the solvent was removed in-vacuo and the remaining residue was dissolved with water (1 ml) and 1N HCl was added dropwise (9 drops) until precipitation stopped. The fine pale-yellow solid was collected by vacuum filtration. LCMS and HPLC showed 100% purity and NMR supports the desired structure. The product, 6-bromo-3-fluoro-1-isopropyl-1H-indole-4-carboxylic acid (24 mg, 0.080 mmol, 76% yield), was obtained as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (br. s., 1H), 8.12 (t, J=1.89 Hz, 1H), 7.77 (d, J=2.27 Hz, 1H), 7.66 (d, J=1.77 Hz, 1H), 4.88 (qd, J=5.31, 6.65 Hz, 1H), 1.40 (d, 6H). MS (ES) [M+H]+ 300.1.

Source