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Hydrogen Peroxide → dibenzyl 3,3-difluoro-1-((2-methoxy-4-(2-oxo-3-(4-(trifluoromethoxy)phenylthio)pyrazin-1(2H)-yl)phenoxy)methyl)cyclobutyl phosphate

HRID 562593
ノート
印刷プレビュー

反応式

HRID 562593 の反応式
C(N(C(C)C)[P:5]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(C)C.[F:25][C:26]1([F:60])[CH2:29][C:28]([CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]3[CH:44]=[CH:43][N:42]=[C:41]([S:45][C:46]4[CH:51]=[CH:50][C:49]([O:52][C:53]([F:56])([F:55])[F:54])=[CH:48][CH:47]=4)[C:40]3=[O:57])=[CH:35][C:34]=2[O:58][CH3:59])([OH:30])[CH2:27]1.N1C=NC=N1.[OH:66]O>ClCCCl.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>[P:5]([O:30][C:28]1([CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]3[CH:44]=[CH:43][N:42]=[C:41]([S:45][C:46]4[CH:47]=[CH:48][C:49]([O:52][C:53]([F:55])([F:54])[F:56])=[CH:50][CH:51]=4)[C:40]3=[O:57])=[CH:35][C:34]=2[O:58][CH3:59])[CH2:29][C:26]([F:25])([F:60])[CH2:27]1)([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:66]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 784Hydrogen PeroxideHCID 92571H-1,2,4-TriazoleHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 575405201-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)-3-(4-(trifluoromethoxy)phenylthio)pyrazin-2(1H)-one

生成物 1

HCID 57540648dibenzyl 3,3-difluoro-1-((2-methoxy-4-(2-oxo-3-(4-(trifluoromethoxy)phenylthio)pyrazin-1(2H)-yl)phenoxy)methyl)cyclobutyl phosphate
収率 77%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒HCID 24477Sodium Thiosulfate溶媒

実験手順

To a mixture of dibenzyl diisopropylphosphoramidite (135 mg, 0.390 mmol), 1-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)-3-(4-(trifluoromethoxy)phenylthio)pyrazin-2(1H)-one (Example 75) (69 mg, 0.130 mmol) and 1H-1,2,4-triazole (27.0 mg, 0.390 mmol) in DCE (20 mL) was stirred at reflux for 6 hours. The mixture was cooled to RT. 30% hydrogen peroxide in water (10 ml) was slowly added and the mixture was stirred at RT for 30 min. The mixture was diluted with a solution of aqueous 10% sodium thiosulfate (40 ml) and was extracted with DCM (50 ml). The DCM layer was dried over sodium sulfate and concentrated. The crude product was purified by ISCO silica gel Column (40 g) and the product was eluted with hexane to 100% ethyl acetate in 10 min. Yield dibenzyl 3,3-difluoro-1-((2-methoxy-4-(2-oxo-3-(4-(trifluoromethoxy)phenylthio)pyrazin-1(2H)-yl)phenoxy)methyl)cyclobutyl phosphate (79 mg, 0.100 mmol, 77% yield) as off-white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.57-7.66 (2H, m), 7.27-7.39 (12H, m), 7.13 (1H, d, J=4.53 Hz), 6.81-7.00 (4H, m), 4.97-5.14 (4H, m), 4.29 (2H, s), 3.75 (3H, s), 2.93-3.20 (4H, m).

後処理

  1. temperatureat reflux for 6 hours
  2. stirringthe mixture was stirred at RT for 30 min
  3. extractionwas extracted with DCM (50 ml)
  4. dry with materialThe DCM layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by ISCO silica gel Column (40 g)
  7. washthe product was eluted with hexane to 100% ethyl acetate in 10 min

出典と根拠

ORDレコード
ord-74c62050b61e48cbbfe280586091e320
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08067420B2

反応ノート

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