Trifluoroacetic acid → {6-[4-(4-Trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-2,3-dihydroindol-1-yl}-acetic acid methyl ester

HRID 2110141Notes

Reaction equation

HRID 2110141 reaction equation
C([SiH](CC)CC)C.[CH3:8][O:9][C:10](=[O:41])[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([S:21]([N:24]3[CH2:29][CH2:28][N:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=4)[CH2:26][CH2:25]3)(=[O:23])=[O:22])[CH:19]=2)[CH:14]=[CH:13]1.FC(F)(F)C(O)=O>[OH-].[Na+]>[CH3:8][O:9][C:10](=[O:41])[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([S:21]([N:24]3[CH2:29][CH2:28][N:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:39])([F:40])[F:38])=[CH:32][CH:31]=4)[CH2:26][CH2:25]3)(=[O:23])=[O:22])[CH:19]=2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052Triethylsilane2×HCID 67045834HCID 67045834, compound

Product 1

HCID 67045986{6-[4-(4-Trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-2,3-dihydroindol-1-yl}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

Triethylsilane (0.13 mL, 0.77 mmol) was added to a solution of {6-[4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indol-1-yl}-acetic acid methyl ester (82 mg, 0.16 mmol) and trifluoroacetic acid (4 mL) at rt. After 1 h, more triethylsilane (0.2 mL, 1.2 mmol) was added. After an additional 4 h, the reaction was poured into 1.2 M NaOH (50 mL) and extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried, filtered, concentrated and purified by silica gel chromatography (4:1→3:2; hexanes:ethyl acetate) to give {6-[4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-2,3-dihydroindol-1-yl}-acetic acid methyl ester: MS (ESI): 500.1 (M+H). {6-[4-(4-Trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-2,3-dihydro-indol-1-yl}-acetic acid methyl ester was hydrolyzed following the procedure outlined in Example 1 Step 2 to give {6-[4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-2,3-dihydro-indol-1-yl}-acetic acid: 1H NMR (400 MHz, DMSO-d6): δ 7.24 (d, 1H), 7.19 (d, 2H), 6.98 (d, 2H), 6.93 (d, 1H), 6.68 (s, 1H), 4.05 (s, 2H), 3.57 (t, 2H), 3.24-3.17 (m, 4H), 3.03 (t, 2H), 3.00-2.94 (m, 4H); MS (ESI): 486.1 (M+H).

Workup

  1. waitAfter an additional 4 h
  2. extractionextracted with CH2Cl2 (3×30 mL)
  3. customThe combined organic extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (4:1→3:2; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-646f03934d744188bd1bccde8eb8bd67
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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