Lithium Hydroxide → 5-(6-Methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylic acid

HRID 2391587Notes

Reaction equation

HRID 2391587 reaction equation
COC1N=CC2N(C3SC(C(OC)=O)=C(OCC4C=CC=CC=4C(F)(F)F)C=3)C=NC=2C=1.[CH3:33][O:34][C:35]1[N:40]=[CH:39][C:38]2[N:41]=[CH:42][N:43]([C:44]3[S:48][C:47]([C:49]([O:51]C)=[O:50])=[C:46]([O:53][CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=4[C:61]([F:64])([F:63])[F:62])[CH:45]=3)[C:37]=2[CH:36]=1.[Li+].[OH-].[OH-].[Na+]>O1CCCC1.C(OCC)C>[CH3:33][O:34][C:35]1[N:40]=[CH:39][C:38]2[N:41]=[CH:42][N:43]([C:44]3[S:48][C:47]([C:49]([OH:51])=[O:50])=[C:46]([O:53][CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=4[C:61]([F:64])([F:62])[F:63])[CH:45]=3)[C:37]=2[CH:36]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 68766502methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylateHCID 68768085methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate

Product 1

HCID 251532845-(6-Methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.2 g of an isomeric mixture of methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate and methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compounds B6a and B6b) in 30 ml tetrahydrofuran were added dropwise 30 ml of a 1N solution of LiOH. The reaction mixture was stirred for 12 h at room temperature and poured into a mixture of 200 ml diethylether and 0.1 N NaOH (1:1). The organic and aqueous layers were separated and the aqueous layer was acidified with HCl until pH 2 was reached. The aqueous layer was extracted with ethyl acetate (2×50 ml). The combined organic layers were dried with MgSO4 and concentrated to dryness under vacuum. The residue was purified by preparative HPLC to yield the title compound. The structural assignment of the title compound was unequivocally established by two-dimensional 1H NMR experiments (NOESY, COSY).

Workup

  1. customThe organic and aqueous layers were separated
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 ml)
  3. dry with materialThe combined organic layers were dried with MgSO4
  4. concentrationconcentrated to dryness under vacuum
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c5f18bf9cf7844b78032f73ef28b74d3
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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