Dimethylformamide → 2-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide

HRID 1624286ノート

反応式

HRID 1624286 の反応式
[CH3:1][N:2]([CH3:15])[S:3]([N:6]1[C:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C:9]=2[N:8]=[CH:7]1)(=[O:5])=[O:4].C([Li])CCC.CN([CH:24]=[O:25])C.[NH4+].[Cl-]>C1COCC1>[CH3:1][N:2]([CH3:15])[S:3]([N:6]1[C:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C:9]=2[N:8]=[C:7]1[CH:24]=[O:25])(=[O:4])=[O:5]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 69156673N,N-Dimethyl-4,5,6,7-tetrahydro-1H-benzimidazole-1-sulfonamideHCID 178418339Butyllithium

生成物 1

HCID 865903112-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide収率 51.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

2-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide was prepared following a modification of the procedure found in the Journal of Medicinal Chemistry, 40; 14, 1997, 2205. To a solution of 4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide (2.67 g, 11.6 mmol) in dry THF (100 mL) under argon at −78° C. was added dropwise 2.5 M n-butyllithium in hexanes (7.0 mL, 17.5 mmol). The reaction was stirred at −78° C. for 1 hour, then DMF (1.1 mL, 13.9 mmol) was added dropwise, and the reaction was warmed to room temperature and stirred for 2 hours. Saturated NH4Cl (25 mL) was added, and the reaction mixture was concentrated, and then diluted with CH2Cl2 (500 mL) and distilled water (25 mL). The layers were separated and the aqueous phase was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were washed with brine (1×100 mL), dried (Na2SO4), and concentrated. Purification of the crude material by column chromatography on silica gel (1:1 hexanes-EtOAc) provided 1.53 g (51%) of 2-formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide as a yellow solid. 1H NMR (CDCl3) δ 1.82-1.86 (m, 4H), 2.66-2.68 (m, 2H), 2.86-2.88 (m, 2H), 2.96 (s, 6H), 9.99 (s, 1H).

後処理

  1. custom2-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide was prepared
  2. temperaturethe reaction was warmed to room temperature
  3. stirringstirred for 2 hours
  4. concentrationthe reaction mixture was concentrated
  5. additiondiluted with CH2Cl2 (500 mL)
  6. distillationdistilled water (25 mL)
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with CH2Cl2 (2×100 mL)
  9. washThe combined organic extracts were washed with brine (1×100 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customPurification of the crude material by column chromatography on silica gel (1:1 hexanes-EtOAc)

出典と根拠

ORDレコード
ord-bba2947ef2504bd3b8c19055036ecbd1
出典データセット
uspto-grants-2014_07
特許番号
US08778967B2

反応ノート

読み込み中…