HCID 67153303、化合物 → 2-(3-formyl-benzyl)-1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide

HRID 1879473ノート

反応式

HRID 1879473 の反応式
[CH3:1][C@@H:2]1[C@@H:7]([NH:8][C:9]([CH:11]2[CH2:15][CH2:14][S:13](=[O:17])(=[O:16])[N:12]2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]#N)[CH:20]=2)=[O:10])[CH2:6][C@H:5]2[CH2:27][C@@H:3]1[C:4]2([CH3:29])[CH3:28].O.P(P([O-])([O-])=O)([O-])([O-])=[O:32].[Na+].[Na+].[Na+].[Na+]>N1C=CC=CC=1CC(O)=O.O.[Ni]>[CH3:1][C@@H:2]1[C@@H:7]([NH:8][C:9]([CH:11]2[CH2:15][CH2:14][S:13](=[O:17])(=[O:16])[N:12]2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=[O:32])[CH:20]=2)=[O:10])[CH2:6][C@H:5]2[CH2:27][C@@H:3]1[C:4]2([CH3:29])[CH3:28]

参加物

5

反応物 2

HCID 67153303HCID 67153303、化合物HCID 131730070HCID 131730070、化合物

生成物 1

HCID 872885452-(3-formyl-benzyl)-1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide収率 49.8%

試薬・触媒・溶媒 2

HCID 935Nickel触媒HCID 69477857Pyridine-acetic acid water溶媒

反応条件

温度
0 °C

実験手順

To a stirred solution of 2-(3-cyano-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.200 g, 0.48 mmol) in a mixture of pyridine-acetic acid-water (2:1:1; 7.2 mL) was added sodium hypophosphate hydrate (0.400 g, 3.77 mmol) at room temperature. The reaction mixture was cooled to 0° C. and Raney Nickel (0.200 g) was added under an argon atmosphere. After stirring at 0° C. for 10 min, the temperature was raised to 40-45° C. and the reaction mixture was stirred for an additional 2.5 h at the same temperature (with monitoring by silica TLC). The reaction mixture was cooled, filtered through a pad of celite and the residue was washed with methanol (5 mL). The combined filtrates were concentrated to provide the crude material, which was purified by silica gel column chromatography (100-200 mesh) using a gradient of 50-60% ethyl acetate/hexanes to give 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.100 g, 49%).

後処理

  1. temperaturethe temperature was raised to 40-45° C.
  2. stirringthe reaction mixture was stirred for an additional 2.5 h at the same temperature (with monitoring by silica TLC)
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered through a pad of celite
  5. washthe residue was washed with methanol (5 mL)
  6. concentrationThe combined filtrates were concentrated
  7. customto provide the crude material, which
  8. customwas purified by silica gel column chromatography (100-200 mesh)

出典と根拠

ORDレコード
ord-de4527d00b954805b749579f14c08f31
出典データセット
uspto-grants-2012_11
特許番号
US08314250B2

反応ノート

読み込み中…