Hydrochloric Acid → 2-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515704Notes

Reaction equation

HRID 515704 reaction equation
[CH:1]([O:4][C:5]1[CH:32]=[CH:31][C:8]([CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][CH:22]([CH2:23][C:24]([O:26]C(C)(C)C)=[O:25])[C:15]4=[CH:14][C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:33]([F:36])([F:35])[F:34])([CH3:3])[CH3:2].[Li+].[OH-].Cl>>[CH:1]([O:4][C:5]1[CH:32]=[CH:31][C:8]([CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][CH:22]([CH2:23][C:24]([OH:26])=[O:25])[C:15]4=[CH:14][C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:33]([F:36])([F:34])[F:35])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67248886tert-Butyl 2-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 583296112-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 36.9%

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 2-(7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.418 g, 0.830 mmol) in dioxanes (10 mL) was added 1.0 M solution of LiOH (aq, 2.5 mL). The reaction was stirred at 70° C. for 4 h and acidified with 1M HCl (aq) to pH 3.0. The mixture was extracted with EtOAc, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a yellow solid (137 mg). LCMS m/z=448.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=5.94 Hz, 6H), 2.15-2.26 (m, 1H), 2.51-2.59 (m, 1H), 2.64-2.72 (m, 1H), 2.72-2.82 (m, 1H), 3.53-3.63 (m, 1H), 3.91-4.00 (m, 1H), 4.05-4.14 (m, 1H), 4.74-4.82 (m, 1H), 5.05 (s, 2H), 6.01 (s, 1H), 6.75 (dd, J=8.72, 2.40 Hz, 1H), 7.06 (d, J=2.27 Hz, 1H), 7.18 (d, J=8.84 Hz, 1H), 7.26-7.32 (m, 1H), 7.63-7.69 (m, 2H), 12.28 (bs, 1H).

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-32176d19838545a7b010e6002df9a52c
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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