Trifluoroacetic acid → 2-(6-Chloro-3-((3-(ethoxycarbonyl)-2-fluorophenyl) thio)-7-fluoro-2-methyl-1H-indol-1-yl) acetic acid

HRID 2171305Notes

Reaction equation

HRID 2171305 reaction equation
C([O:5][C:6](=[O:33])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:18])[C:15]=2[F:17])[C:10]([S:19][C:20]2[C:21]([F:31])=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:9]1[CH3:32])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:18][C:14]1[C:15]([F:17])=[C:16]2[C:11]([C:10]([S:19][C:20]3[CH:30]=[CH:29][CH:28]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:21]=3[F:31])=[C:9]([CH3:32])[N:8]2[CH2:7][C:6]([OH:33])=[O:5])=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117979167Ethyl 3-((1-(2-(tert-butoxy)-2-oxoethyl)-6-chloro-7-fluoro-2-methyl-1H-indol-3-yl) thio)-2-fluorobenzoate

Product 1

HCID 1179905162-(6-Chloro-3-((3-(ethoxycarbonyl)-2-fluorophenyl) thio)-7-fluoro-2-methyl-1H-indol-1-yl) acetic acidYield 84.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of compound 5 (200 mg, 0.40 mmol) in CH2Cl2 (10 mL) under inert atmosphere was added TFA (0.8 mL) at 0° C.; warmed to RT and stirred for 12 h. The reaction was monitored by TLC; after completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water (20 mL) and extracted with CH2Cl2 (2×30 mL). The combined organic extracts were washed with water (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was triturated with n-pentane (2×5 mL) to afford compound 6 (149 mg, 81%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.59-7.55 (m, 1H), 7.19-7.06 (m, 3H), 6.79-6.75 (m, 1H), 4.93 (s, 2H), 4.32 (q, 2H), 2.40 (s, 3H), 1.31 (t, J=7.2 Hz, 3H); LC-MS: 98.7%; 440.3 (M++1); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 2.90 min. 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. customafter completion of the reaction
  2. customthe volatiles were removed under reduced pressure
  3. additionThe residue was diluted with water (20 mL)
  4. extractionextracted with CH2Cl2 (2×30 mL)
  5. washThe combined organic extracts were washed with water (15 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain the crude
  10. customThe crude was triturated with n-pentane (2×5 mL)

Sources & evidence

ORD record
ord-5cb62b7fe0494df88c14e88af4812d9d
Source dataset
uspto-grants-2015_06
Patent number
US09051320B1

Reaction notes

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