Acetic Acid → Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid

HRID 417111ノート

反応式

HRID 417111 の反応式
C(N(N=O)[C:9](=[O:38])[CH:10]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[N:11]1[C:15]2[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=2[N:13]=[C:12]1[C:22]1[C:23]([O:30][CH3:31])=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1)C1C=CC=CC=1.O.[OH-].[Li+].OO.C(O)(=[O:48])C>O1CCCC1.O>[CH:32]1([CH:10]([N:11]2[C:15]3[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C:22]2[C:23]([O:30][CH3:31])=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)[C:9]([OH:38])=[O:48])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 86639899N-benzyl-N-nitroso-2-cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetamide

生成物 1

HCID 66619285Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of 12.1 g (22.02 mmol) N-benzyl-N-nitroso-2-cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetamide in 65 ml tetrahydrofuran and 15 ml water were added dropwise over 20 min. a solution of 9.24 g (220 mmol) lithium hydroxide monohydrate in 45 ml (440 mmol) hydrogen peroxide and 30 ml water. The reaction mixture turned into a turbid solution and a slight temperature raise was observed (cooled temporarily using an ice-bath). After 1 h the pH of the mixture was adjusted to pH 4 using acetic acid. The resulting light yellow solution was extracted three times with ethyl acetate. The combined organic layers were washed twice with saturated aqueous sodium bicarbonate solution, once with water and once with brine. The solution was dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in 200 ml tert-butyl methyl ether and partially evaporated until a precipitation formed. The suspension was cooled in the refrigerator for 30 min, then the solid was filtered off, washed with 50 ml ice-cold tert-butyl methyl ether and dried in high vacuum. White solid (99%). MS (Turbo Spray): m/z=432.2 [M+H].

後処理

  1. temperaturea slight temperature raise
  2. temperaturecooled temporarily
  3. extractionThe resulting light yellow solution was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed twice with saturated aqueous sodium bicarbonate solution, once with water and once with brine
  5. dry with materialThe solution was dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in 200 ml tert-butyl methyl ether
  9. custompartially evaporated until a precipitation
  10. customformed
  11. temperatureThe suspension was cooled in the refrigerator for 30 min
  12. filtrationthe solid was filtered off
  13. washwashed with 50 ml ice-cold tert-butyl methyl ether
  14. customdried in high vacuum

出典と根拠

ORDレコード
ord-9c2f1b6d1d7f43a287107670cac0681f
出典データセット
uspto-grants-2012_01
特許番号
US08088930B2

反応ノート

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