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

HRID 2391587ノート

反応式

HRID 2391587 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c5f18bf9cf7844b78032f73ef28b74d3
出典データセット
uspto-grants-2012_09
特許番号
US08273890B2

反応ノート

読み込み中…