Lithium Hydroxide → 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515713Notes

Reaction equation

HRID 515713 reaction equation
[CH:1]1([C:6]2[CH:30]=[CH:29][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[NH:17][C:16]5[CH:21]([CH2:24][C:25]([O:27]C)=[O:26])[CH2:22][CH2:23][C:15]=5[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:31]([F:34])([F:33])[F:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Li+].O1CCOC[CH2:38]1>>[CH:1]1([C:6]2[CH:30]=[CH:29][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:23][CH2:22][CH:21]([CH2:24][C:25]([OH:27])=[O:26])[C:16]5=[C:15]([CH3:38])[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:31]([F:32])([F:33])[F:34])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 3939Lithium HydroxideHCID 312751,4-DioxaneHCID 67250606Methyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

Product 1

HCID 583295742-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Conditions

Temperature
60 °C

Procedure

Methyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (0.579 g, 1.192 mmol) was dissolved in 1,4-dioxane (10.74 mL). Aqueous 1.0 M lithium hydroxide (3.58 mL, 3.58 mmol) was added at 25° C. to give a slightly turbid solution. The reaction mixture was stirred at 60° C. for 1 h and cooled to 25° C. The solvent was evaporated in vacuo at 25° C. to a volume of 4 mL and added 0.5 M citric acid (14 mL) and MTBE (75 mL). The mixture was shaken. The organic layer was separated, washed with H2O (2×20 mL), brine (20 mL), and dried over MgSO4. The solvent was evaporated in vacuo to give the title compound (0.540 g) as white crystals. LCMS m/z=472.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.73 (m, 4H), 1.79-1.90 (m, 2H), 2.01 (m, 2H), 2.15 (s, 3H), 2.19-2.29 (m, 1H), 2.40-2.48 (m, 1H), 2.70-2.82 (m, 2H), 3.20-3.28 (m, 1H), 3.60 (m, 1H), 3.92 (m, 1H), 4.03 (m, 1H), 5.14 (s, 2H), 6.76 (dd, J=8.72, 2.40 Hz, 1H), 7.02 (d, J=2.40 Hz, 1H), 7.14 (d, J=8.72 Hz, 1H), 7.63 (d, J=8.00 Hz, 1H), 7.68-7.76 (m, 2H), 12.26 (bs, 1H).

Workup

  1. customto give a slightly turbid solution
  2. temperaturecooled to 25° C
  3. customThe solvent was evaporated in vacuo at 25° C. to a volume of 4 mL
  4. additionadded 0.5 M citric acid (14 mL) and MTBE (75 mL)
  5. stirringThe mixture was shaken
  6. customThe organic layer was separated
  7. washwashed with H2O (2×20 mL), brine (20 mL)
  8. dry with materialdried over MgSO4
  9. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-d4537603427d429182ea2edc4c0f6c12
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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