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

HRID 1964122Notes

Reaction equation

HRID 1964122 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 1 M 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-67c57f32730b4ec0bf975afa11c9484d
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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