Sodium Azide → (1R,2S,7R,8S)-5-(7-azido-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

HRID 424228ノート

反応式

HRID 424228 の反応式
[F:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26](I)=[CH:27][C:21]=4[S:20](=[O:30])(=[O:29])[N:19]=3)=[C:14]([OH:31])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:32][C@@H:12]3[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[N-:35]=[N+:36]=[N-:37].[Na+].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].CN[C@@H]1CCCC[C@H]1NC>CS(C)=O.O.[Cu]I>[N:35]([C:26]1[CH:25]=[CH:24][C:22]2[NH:23][C:18]([C:15]3[C:16](=[O:17])[N:7]([CH2:6][C:5]4[CH:33]=[CH:34][C:2]([F:1])=[CH:3][CH:4]=4)[C@@H:8]4[C@H:13]([C:14]=3[OH:31])[C@@H:12]3[CH2:32][C@H:9]4[CH2:10][CH2:11]3)=[N:19][S:20](=[O:30])(=[O:29])[C:21]=2[CH:27]=1)=[N+:36]=[N-:37]

参加物

8

反応物 4

HCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 23667548Sodium AscorbateHCID 136395898(1R,2S,7R,8S)-3-(4-Fluoro-benzyl)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

生成物 1

HCID 136404886(1R,2S,7R,8S)-5-(7-azido-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one収率 79.2%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
25 °C

実験手順

(1R,2S,7R,8S)-3-(4-Fluoro-benzyl)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 19, 0.513 g, 0.864 mmol), sodium azide (1.12 g, 17.2 mmol), sodium ascorbate (0.086 g, 0.43 mmol), copper (I) iodide (0.16 g, 0.84 mmol), and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.20 mL, 1.27 mmol) were dissolved in a 5:1 mixture of dimethyl sulfoxide and water (10 mL) at 25° C. The reaction flask was degassed and backfilled with nitrogen (5×). After stirring at 25° C. for 14 h, the reaction mixture was partitioned between water (150 mL) and ethyl acetate (2×150 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 60% ethyl acetate in hexanes) to afford the desired product, (1R,2S,7R,8S)-5-(7-azido-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.348 g, 0.684 mmol, 79%), as a dark brown foam, which was used in the next step without any further purification.

後処理

  1. customThe reaction flask was degassed
  2. customthe reaction mixture was partitioned between water (150 mL) and ethyl acetate (2×150 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 60% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-cb80eea7c75a4f9d8437b6ceb63dce5b
出典データセット
uspto-grants-2012_01
特許番号
US08101800B2

反応ノート

読み込み中…