Water → 2-(7-(4-Cyclohexyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic Acid

HRID 2040539Notes

Reaction equation

HRID 2040539 reaction equation
Cl[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][C:14]3[NH:13][C:12]4[CH:17]([CH2:20][C:21]([O:23]CC)=[O:22])[CH2:18][CH2:19][C:11]=4[C:10]=3[CH:9]=2)=[CH:4][C:3]=1[C:28]([F:31])([F:30])[F:29].[Br-].[CH:33]1([Zn+])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.O.O[Li].O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CO>[CH:33]1([C:2]2[CH:27]=[CH:26][C:5]([CH2:6][O:7][C:8]3[CH:16]=[CH:15][C:14]4[NH:13][C:12]5[CH:17]([CH2:20][C:21]([OH:23])=[O:22])[CH2:18][CH2:19][C:11]=5[C:10]=4[CH:9]=3)=[CH:4][C:3]=2[C:28]([F:29])([F:31])[F:30])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 67211075Ethyl 2-(7-(4-Chloro-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetateHCID 178418970HCID 178418970, compound

Product 1

HCID 446239972-(7-(4-Cyclohexyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic AcidYield 27.5%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of ethyl 2-(7-(4-chloro-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (50 mg, 0.111 mmol), 0.5 M cyclohexylzinc(II) bromide (0.5 M in THF, 3 mL, 1.5 mmol), and bis(tri-t-butylphosphine)palladium (3 mg, 5.87 μmol) were stirred under reflux for 18 h. The mixture was allowed to cool to room temperature before water (1 mL), MeOH (1 mL) and LiOH hydrate (70 mg, 1.668 mmol) were added. The mixture was stirred at room temperature for 2 h. The mixture was purified by HPLC. Fractions containing product were basified with 1 M NaHCO3 and partially concentrated. The residue was extracted with 0.5 M citric acid and CH2Cl2. The organics were dried over MgSO4, filtered and concentrated to give the title compound as a tanned sticky solid (14.4 mg). LCMS m/z=472.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.38-1.50 (m, 4H), 1.76-1.85 (m, 6H), 2.11-2.17 (m, 1H), 2.58-2.65 (m, 1H), 2.75-2.93 (m, 5H), 3.56-3.60 (m, 1H), 5.07 (s, 2H), 6.84 (dd, J=8.8, 2.5 Hz, 1H), 7.00 (d, J=2.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.59 (d, J=8.1 Hz, 1H), 7.70 (d, J=1.2 Hz, 1H), 8.27 (s, 1H).

Workup

  1. temperatureunder reflux for 18 h
  2. additionwere added
  3. stirringThe mixture was stirred at room temperature for 2 h
  4. customThe mixture was purified by HPLC
  5. additionFractions containing product
  6. concentrationpartially concentrated
  7. extractionThe residue was extracted with 0.5 M citric acid and CH2Cl2
  8. dry with materialThe organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-58457c816a024de6baf7e72631a875e0
Source dataset
uspto-grants-2013_11
Patent number
US08580841B2

Reaction notes

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