Lithium Hydroxide → 2-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515708Notes

Reaction equation

HRID 515708 reaction equation
[CH:1]([O:4][C:5]1[CH:33]=[CH:32][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=[C:14]([CH3:31])[C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:34]([F:37])([F:36])[F:35])([CH3:3])[CH3:2].[Li+].[OH-]>CCOC(C)=O>[CH:1]([O:4][C:5]1[CH:33]=[CH:32][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=[C:14]([CH3:31])[C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:34]([F:37])([F:35])[F:36])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67249074tert-Butyl 2-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 583295822-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 95.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl 2-(7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.366 g, 0.707 mmol) in dioxanes was added aq LiOH (3.0 mmol). The reaction was stirred at 75° C. for 16 h, diluted with EtOAc and washed with 1M HCl(aq), dried over MgSO4, filtered, and concentrated. The residue was triturated with hexanes to give the title compound as a solid (0.313 g). LCMS m/z=462.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=5.94 Hz, 6H), 2.15 (s, 3H), 2.19-2.29 (m, 1H), 2.42-2.48 (m, 1H), 2.69-2.82 (m, 2H), 3.57-3.65 (m, 1H), 3.86-3.97 (m, 1H), 3.97-4.08 (m, 1H), 4.73-4.84 (m, 1H), 5.07 (s, 2H), 6.74 (dd, J=8.72, 2.40 Hz, 1H), 7.01 (d, J=2.40 Hz, 1H), 7.13 (d, J=8.59 Hz, 1H), 7.29 (d, J=9.22 Hz, 1H), 7.64-7.72 (m, 2H), 12.26 (bs, 1H).

Workup

  1. washwashed with 1M HCl(aq)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was triturated with hexanes

Sources & evidence

ORD record
ord-9aaf924bff9641cfaf909aa1284efd71
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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