Pyridinium, 1-fluoro-, 1,1,1-trifluoromethanesulfonate (1:1) → 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-(pyridin-2-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515714Notes

Reaction equation

HRID 515714 reaction equation
[CH:1]1([C:6]2[CH:29]=[CH:28][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:16]5=[CH:15][C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:30]([F:33])([F:32])[F:31])[CH2:5][CH2:4][CH2:3][CH2:2]1.[O-]S(C(F)(F)F)(=O)=O.F[N+:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(Cl)Cl.CCOC(C)=O>[CH:1]1([C:6]2[CH:29]=[CH:28][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:16]5=[C:15]([C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][N:43]=5)[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:30]([F:33])([F:31])[F:32])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 2724576Pyridinium, 1-fluoro-, 1,1,1-trifluoromethanesulfonate (1:1)HCID 461749052-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Product 1

HCID 583296032-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-(pyridin-2-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 9.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The 1st enantiomer (described as the enantiomer isolated and having the retention time of 15 min per the conditions reported in Example 1.7) of 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid (0.100 g, 0.219 mmol) was dissolved in anhydrous DCM (2.2 mL) using a plastic vial. The reaction was cooled to 0° C., and N-fluoropyridinium triflate (0.073 g, 0.295 mmol) was added. The reaction was allowed to warm to 25° C. and after 4 h there was a dark solution. The reaction was diluted with EtOAc (40 mL), washed with water/brine (2×10 mL), brine (10 mL), and dried over MgSO4. The solvent was evaporated in vacuo. The residue was purified by HPLC to give the titled compound (0.011 g) as a yellow solid. LCMS m/z=535.5 [M+H]+; 1H NMR (400 MHz, CD3CN) δ ppm 1.54-1.78 (m, 4H), 1.79-1.92 (m, 2H), 2.05 (dd, J=9.92, 4.48 Hz, 2H), 2.43-2.53 (m, 2H), 2.57-2.73 (m, 2H), 3.29-3.41 (m, 1H), 4.09-4.28 (m, 3H), 5.17 (d, J=3.54 Hz, 2H), 6.99 (dd, J=8.84, 2.27 Hz, 1H), 7.34 (d, J=8.84 Hz, 1H), 7.44 (d, J=2.27 Hz, 1H), 7.53 (t, J=6.25 Hz, 1H), 7.56-7.61 (m, 1H), 7.64-7.69 (m, 1H), 7.73 (s, 1H), 7.90 (d, J=8.34 Hz, 1H), 8.23 (td, J=7.86, 1.58 Hz, 1H), 8.66 (d, J=4.42 Hz, 1H).

Workup

  1. customisolated
  2. temperatureto warm to 25° C. and after 4 h there
  3. washwashed with water/brine (2×10 mL), brine (10 mL)
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-296d21d08cb649ba9307d1b2bec7d84b
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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