Citric Acid → 2-(2-(3-Cyano-5-(trifluoromethoxy)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic Acid

HRID 1964168Notes

Reaction equation

HRID 1964168 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][C:31]([F:34])([F:33])[F:32])[CH:29]=1)[CH2:6][O:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]1[CH2:17][CH2:18][CH2:19][CH:20]([CH2:21][C:22]([O:24]CC)=[O:23])[C:12]1=[CH:11]2)#[N:2].[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1.O>[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][C:31]([F:34])([F:32])[F:33])[CH:29]=1)[CH2:6][O:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]1[CH2:17][CH2:18][CH2:19][CH:20]([CH2:21][C:22]([OH:24])=[O:23])[C:12]1=[CH:11]2)#[N:2]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 67248872Ethyl 2-(2-(3-Cyano-5-(trifluoromethoxy)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate

Product 1

HCID 583296172-(2-(3-Cyano-5-(trifluoromethoxy)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic AcidYield 88.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ethyl 2-(2-(3-cyano-5-(trifluoromethoxy)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate (108 mg, 0.229 mmol) in dioxane (1 mL) was added 1 M LiOH aqueous solution (0.914 mL, 0.914 mmol). The reaction was stirred at room temperature for 8 h, diluted with water, and acidified to pH 4 with 0.5 M aqueous citric acid. The solid precipitate was collected to give the title compound (90 mg). LCMS m/z=445.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.57-1.68 (m, 1H), 2.00-2.14 (m, 1H), 2.16-2.27 (m, 2H), 2.65 (dd, J=16.1, 8.5 Hz, 1H), 3.01 (dd, J=16.1, 5.4 Hz, 1H), 3.46-3.55 (m, 1H), 3.85-3.93 (m, 1H), 4.13-4.20 (m, 1H), 5.13 (s, 2H), 6.23 (s, 1H), 6.89 (dd, J=8.8, 2.4 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H), 7.19 (d, J=8.8 Hz, 1H), 7.44 (s, 1H), 7.58 (s, 1H), 7.70 (s, 1H).

Workup

  1. customThe solid precipitate was collected

Sources & evidence

ORD record
ord-ba171da6d0d5422cb88a19c37d90f640
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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