Hydrochloric Acid → (3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetic acid

HRID 12606Notes

Reaction equation

HRID 12606 reaction equation
[C:1]1([C:7]2[C:15]3[CH2:14][CH2:13][CH2:12][CH:11]([CH2:16][C:17]([O:19]CC)=[O:18])[C:10]=3[N:9]([CH:22]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)[CH2:23][CH2:24][CH3:25])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Li+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[C:1]1([C:7]2[C:15]3[CH2:14][CH2:13][CH2:12][CH:11]([CH2:16][C:17]([OH:19])=[O:18])[C:10]=3[N:9]([CH:22]([C:26]3[CH:27]=[CH:28][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:30][CH:31]=3)[CH2:23][CH2:24][CH3:25])[CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86615520HCID 86615520, compound

Product 1

HCID 11597689(3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetic acidYield 55%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of ethyl (3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetate (107 mg, 2.2 mmol) in dioxane (5 ml) and water (0.5 ml) was added lithium hydroxide (900 mg, 22.0 mmol) and the reaction heated to reflux for 16 h. After cooling, the reaction was diluted with ethyl acetate and acidified with 2N HCl. The aqueous layer was extracted three times with ethyl acetate, and the combined organic layers dried over sodium sulfate and concentrated in vacuo. The product was purified by mass directed HPLC to give (3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetic acid (55.1 mg, 55%), a colourless foam as a 1:1 mixture of diastereomers A and B; 1H NMR δ (ppm) (CDCl3): 7.59 (2 H, d, J=8.2 Hz, A/B), 7.53 (2 H, d, J=8.1 Hz, A/B), 7.47 (2 H, d, J=8.1 Hz, A/B), 7.35 (4 H, t, J=7.3 Hz A+B), 7.21-7.13 (4 H, m, A+B), 7.06 (1 H, s, A), 6.95 (1 H, s, B), 5.19-5.11 (2 H, m, A+B), 3.39 (1 H, d, J=9.0 Hz, B), 3.06 (1 H, s, A), 2.79-2.65 (5 H, m, A+B), 2.37-2.19 (2 H, m, A+B), 2.14-2.08 (4 H, m, A+B), 2.00 (1 H, s, A/B), 1.90-1.78 (6 H, t, J=13.5 Hz, A+B), 1.74-1.70 (4 H, m, A+B), 1.42 (1 H, t, J=6.1 Hz, A/B), 1.38-1.30 (1 H, m A/B), 1.03 (3 H, t, J=7.3 Hz, A/B), 0.95 (3 H, t, J=7.3 Hz, A/B); m/z (ES−) 454 (M−H+).

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 16 h
  3. temperatureAfter cooling
  4. extractionThe aqueous layer was extracted three times with ethyl acetate
  5. dry with materialthe combined organic layers dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by mass

Sources & evidence

ORD record
ord-c54bbd9f8a764e4e9a0add2e75bf4c31
Source dataset
uspto-grants-2010_06
Patent number
US07728022B2

Reaction notes

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