Pyrrolidine → Ethyl 2-(7-(4-(Pyrrolidin-1-yl)-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

HRID 2274052Notes

Reaction equation

HRID 2274052 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][CH2:24][CH3:25])=[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].[NH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC([O-])(C)C.[Na+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C>[N:32]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]([O:23][CH2:24][CH3:25])=[O:22])[CH2:18][CH2:19][C:11]=5[C:10]=4[CH:9]=3)=[CH:4][C:3]=2[C:28]([F:31])([F:30])[F:29])[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 67211075Ethyl 2-(7-(4-Chloro-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

Product 1

HCID 67220173Ethyl 2-(7-(4-(Pyrrolidin-1-yl)-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetateYield 32.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of ethyl 2-(7-(4-chloro-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (50.9 mg, 0.113 mmol), pyrrolidine (0.047 mL, 0.563 mmol), diacetoxypalladium (1.264 mg, 5.63 μmol), biphenyl-2-yl-di-tert-butylphosphine (3.36 mg, 11.0 μmol) and sodium 2-methylpropan-2-olate (27.1 mg, 0.282 mmol) in dioxane (3 mL) was heated under microwave irradiation at 120° C. for 2 h. The mixture was purified by HPLC. Fractions containing product were basified with 1 M NaHCO3 and 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 white solid (17.8 mg). LCMS m/z=487.4 [M+H]+.

Workup

  1. customThe mixture was purified by HPLC
  2. additionFractions containing product
  3. concentrationconcentrated
  4. extractionThe residue was extracted with 0.5 M citric acid and CH2Cl2
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3259b711947341bcaf7551f64bf3421c
Source dataset
uspto-grants-2015_09
Patent number
US09126932B2

Reaction notes

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