Phenyl thioxochloroformate → ((2S,3R,5S)-3-(benzoyloxy)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl benzoate

HRID 1278558ノート

反応式

HRID 1278558 の反応式
[C:1]([O:9][C@H:10]1[C@H:14]([CH2:15][O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:13][C@H:12]([N:25]2[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:11]1O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O(C(Cl)=S)C1C=CC=CC=1>ClCCCl.CN(C)C1C=CN=CC=1>[C:1]([O:9][C@H:10]1[C@H:14]([CH2:15][O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:13][C@H:12]([N:25]2[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]2=[O:27])[CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 70498Phenyl thioxochloroformateHCID 667171061-(3,5-Di-O-benzoyi-beta-L-arabinofuranosyl)uracil

生成物 1

HCID 10863035((2S,3R,5S)-3-(benzoyloxy)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl benzoate収率 56%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 111,2-Dichloroethane溶媒

実験手順

To a solution of 1-(3,5-di-O-benzoyl-β-L-arabinofuranosyl)uracil 12 (5.2 g, 11.4 mmoL) in anhydrous 1,2-dichloroethane (120 mL) were added phenoxythiocarbonyl chloride (4.7 mL, 34.3 mL) and 4-(dimethylamino)pyridine (DMAP, 12.5 g, 102.6 mmoL). The resulting solution was stirred at room temperature under argon atmosphere for 1 h and then evaporated under reduced pressure. The residue was dissolved in dichloromethane (300 mL) and the organic solution was successively washed with an ice-cold 0.2 N hydrochloric acid solution (3×200 mL) and water (2×200 mL), dried over Na2SO4 then evaporated under reduced pressure. The crude material was co-evaporated several times with anhydrous dioxane and dissolved in this solvent (110 mL). To the resulting solution were added under argon tris-(trimethylsilyl)silane hydride (4.2 mL, 13.7 mmol) and α,α′-azoisobutyronitrile (AIBN, 0.6 g, 3.76 mmol). The reaction mixture was heated and stirred at 100° C. for 1 h under argon, then cooled to room temperature and evaporated under reduced pressure. The residue was purified by silica gel column chromatography [eluent: stepwise gradient of methanol (0-5%)] to give 13 (2.78 g, 56%) which was crystallized from EtOH: mp=223-225° C.; H-NMR (DMSO-d6): δ11.4 (br s, 1H, NH), 8.0-7.5 (m, 11H, 2 C6H5CO, H-6), 6.28 (t, 1H, H-1′, J=7 Hz), 5.5 (m, 2H, H-1′ and H-5), 4.6-4.4 (m, 3H, H-4′, H-5′ and H-5″), 2.6 (m, 2H, H-2′ and H-2″); MS: FAB>0 (matrix GT) m/z 437 (M+H)+, 3325 (S)+; FAB<0 (matrix GT) m/z 435 (M−H)−, 111 (B)−; Anal. Calcd for C23H20N2O7: C, 63.30; H, 4.62; N, 6.42. Found: C, 62.98; H, 4.79; N, 6.40.

後処理

  1. customevaporated under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane (300 mL)
  3. washthe organic solution was successively washed with an ice-cold 0.2 N hydrochloric acid solution (3×200 mL) and water (2×200 mL)
  4. dry with materialdried over Na2SO4
  5. customthen evaporated under reduced pressure
  6. dissolutiondissolved in this solvent (110 mL)
  7. additionTo the resulting solution were added under argon tris-(trimethylsilyl)silane hydride (4.2 mL, 13.7 mmol)
  8. temperatureThe reaction mixture was heated
  9. stirringstirred at 100° C. for 1 h under argon
  10. temperaturecooled to room temperature
  11. customevaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography [eluent

出典と根拠

ORDレコード
ord-839811742a8441b3ada24cce154d3396
出典データセット
uspto-grants-2002_09
特許番号
US06444652B1

反応ノート

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