Toluene → (1S,2R,4aS,5S,8R,8aR)-2-(acetyloxy)-5-[4-(ethyloxy)-1-methyl-4-oxobut-2-enyl]-8a-hydroxy-3,8-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate

HRID 1727172ノート

反応式

HRID 1727172 の反応式
[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:34])C=O)[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:35])[C@H:20]4[O:36][C:37](=[O:39])[CH3:38])=[O:17])[CH2:15][C@@:7]3([OH:40])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:41]([CH:46]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:43][CH2:44][CH3:45])=[O:42].[C:66]1(C)C=CC=CC=1>>[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:34])[CH:66]=[CH:46][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:35])[C@H:20]4[O:36][C:37](=[O:39])[CH3:38])=[O:17])[CH2:15][C@@:7]3([OH:40])[C:6]=2[CH:5]=[CH:4][CH:3]=1

参加物

4

反応物 3

HCID 1140TolueneHCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 86614045(1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-[1-methyl-2-oxoethyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate

生成物 1

HCID 86614044(1S,2R,4aS,5S,8R,8aR)-2-(acetyloxy)-5-[4-(ethyloxy)-1-methyl-4-oxobut-2-enyl]-8a-hydroxy-3,8-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate収率 6%

実験手順

A solution of ((1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-[1-methyl-2-oxoethyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (Preparation 141, 94 mg, 0.163 mmol) and carbethoxymethylene triphenylphosphorane (68 mg, 0.195 mmol) in anhydrous toluene (5 ml) was refluxed under nitrogen for 3 hours and then stirred at room temperature for 18 h before concentrating in vacuo. The residue was treated with sulfuric acid (10%) and extracted with two aliquots of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated in vacuo. The crude product was taken up in acetonitrile (1 ml), filtered, and purified by preparative HPLC on a Dynamex®, 5 mm×21.6 mm column, eluting with acetonitrile:water (60:40). The pure fractions were concentrated in vacuo to give the title product (7 mg, 6%).

後処理

  1. concentrationbefore concentrating in vacuo
  2. additionThe residue was treated with sulfuric acid (10%)
  3. extractionextracted with two aliquots of ethyl acetate
  4. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered
  8. custompurified by preparative HPLC on a Dynamex®, 5 mm×21.6 mm column
  9. washeluting with acetonitrile:water (60:40)
  10. concentrationThe pure fractions were concentrated in vacuo

出典と根拠

ORDレコード
ord-927fa9d746064ac4847044e06d32cf62
出典データセット
uspto-grants-2009_02
特許番号
US07494992B2

反応ノート

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