Lithium Hydroxide → 2-(2-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic Acid

HRID 1964164Notes

Reaction equation

HRID 1964164 reaction equation
[CH:1]1([C:6]2[CH:32]=[CH:31][C:9]([CH2:10][O:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]3[CH2:21][CH2:22][CH2:23][CH:24]([CH2:25][C:26]([O:28]CC)=[O:27])[C:16]3=[CH:15]4)=[CH:8][C:7]=2[C:33]([F:36])([F:35])[F:34])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-]>O1CCOCC1>[CH:1]1([C:6]2[CH:32]=[CH:31][C:9]([CH2:10][O:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]3[CH2:21][CH2:22][CH2:23][CH:24]([CH2:25][C:26]([OH:28])=[O:27])[C:16]3=[CH:15]4)=[CH:8][C:7]=2[C:33]([F:36])([F:34])[F:35])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67249393Ethyl 2-(2-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate

Product 1

HCID 583296002-(2-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic AcidYield 77.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of ethyl 2-(2-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate (143 mg, 0.286 mmol) in dioxane (1.5 mL) was added 1 M LiOH aqueous solution (1.15 mL, 1.145 mmol). The reaction mixture was stirred at 45° C. for 3 h. A portion of the solvent was removed in vacuo. The remaining mixture was diluted with water, acidified with 0.5 M aqueous citric acid to pH 4, and extracted with ethyl acetate. The combined organics were washed with water, dried over anhydrous Na2SO4, and concentrated to give the title compound (105 mg). LCMS m/z=472.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.54-1.66 (m, 3H), 1.67-1.80 (m, 2H), 1.80-1.92 (m, 2H), 2.00-2.24 (m, 5H), 2.64 (dd, J=16.1 and 8.7 Hz, 1H), 3.01 (dd, J=16.1 and 5.3 Hz, 1H), 3.33-3.42 (m, 1H), 3.45-3.55 (m, 1H), 3.85-3.94 (m, 1H), 4.12-4.18 (m, 1H), 5.08 (s, 2H), 6.22 (s, 1H), 6.90 (dd, J=8.8 and 2.4 Hz, 1H), 7.10 (d, J=2.4 Hz, 1H), 7.17 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H), 7.59 (d, J=8.1 Hz, 1H), 7.70 (s, 1H).

Workup

  1. customA portion of the solvent was removed in vacuo
  2. additionThe remaining mixture was diluted with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organics were washed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-91219aed20484b4687f8477f042c3c53
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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