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

HRID 2040582Notes

Reaction equation

HRID 2040582 reaction equation
[CH:1]1([C:6]2[CH:31]=[CH:30][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]CC)=[O:26])[CH2:22][CH2:23][C:15]=5[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:34])[F:33])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Li+]>O1CCOCC1>[CH:1]1([C:6]2[CH:31]=[CH:30][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]([OH:27])=[O:26])[CH2:22][CH2:23][C:15]=5[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:33])[F:34])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 53345674Ethyl 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

Product 1

HCID 446025042-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic AcidYield 99%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

In a 3 L, 3-necked, round-bottomed flask was placed ethyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (139.4 g, 287 mmol) in dioxane (1.8 L). The mixture was added 2N lithium hydroxide (0.431 L, 861 mmol) and heated to 45-55° C. for 3 h. The mixture was concentrated in vacuo. The residue was added MTBE/water and acidified with concentrated HCl (until pH3) while keeping the temperature under 20° C. with an ice bath. The aqueous layer was separated and extracted with MTBE. The combined organic layers were washed several times with water until pH3 at the end of the washes. Acetonitrile and water were added to the MTBE solution and the mixture was concentrated in vacuo to give the title compound (130 g) without further purification. LCMS m/z=458.4.

Workup

  1. customIn a 3 L, 3-necked, round-bottomed flask was placed
  2. concentrationThe mixture was concentrated in vacuo
  3. additionThe residue was added MTBE/water
  4. customunder 20° C.
  5. customThe aqueous layer was separated
  6. extractionextracted with MTBE
  7. washThe combined organic layers were washed several times with water until pH3 at the end of the washes
  8. additionAcetonitrile and water were added to the MTBE solution
  9. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-dabf431558f74efbb0c67a39f0daf815
Source dataset
uspto-grants-2013_11
Patent number
US08580841B2

Reaction notes

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