Imidazole → HCID 86621229、化合物

HRID 1867914ノート

反応式

HRID 1867914 の反応式
[N:1]([C@@:4]1([CH2:35][O:36][C:37](=[O:45])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[C@@H:8]([O:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:7]([O:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:6]([N:27]2[CH:32]=[CH:31][C:30](=O)[NH:29][C:28]2=[O:34])[O:5]1)=[N+:2]=[N-:3].[NH:46]1[CH:50]=[CH:49][N:48]=[CH:47]1.C(N(CC)CC)C.P(Cl)(Cl)(Cl)=O>CC1OCCC1.O>[N:1]([C@@:4]1([CH2:35][O:36][C:37](=[O:45])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[C@@H:8]([O:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:7]([O:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:6]([N:27]2[CH:32]=[CH:31][C:30]([N:46]3[CH:50]=[CH:49][N:48]=[CH:47]3)=[N:29][C:28]2=[O:34])[O:5]1)=[N+:2]=[N-:3]

参加物

7

反応物 4

HCID 795ImidazoleHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 117072053-chlorobenzoic acid (2R,3S,4R,5R)-2-azido-3,4-bis-benzoyloxy-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester

生成物 1

HCID 86621229HCID 86621229、化合物収率 91.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 73012-Methyltetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

A suspension of 30.0 g (47.5 mmol) 3-chlorobenzoic acid (2R,3S,4R,5R)-2-azido-3,4-bis-benzoyloxy-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester and 26.0 g (380 mmol) imidazole in 110 ml MeTHF was treated at room temperature with 19.2 g (189 mmol) triethylamine. The resulting mixture was treated at 10 to 20° C. within 30 minutes with 11.03 g (71.2 mmol) phosphorous oxychloride. The mixture was heated to 60° C. and stirred at this temperature for 5 hours. The mixture was then cooled to 15° C. and treated at this temperature with 125 ml water. The layers were separated and the aqueous layer was extracted with MeTHF (1×30 ml). From the organic layer MeTHF was completely removed by distillation and replaced by 250 ml acetonitrile. Water (50 ml) and methylene chloride (100 ml) were added and the layers were separated. The aqueous layer was extracted with methylene chloride (1×100 ml). The organic layer was filtered, the solvent was evaporated and the residue (34.2 g) dried in vacuo (<30 mbar) at 40° C. for 16 hours to afford 29.7 g (90.8%) of 3-chlorobenzoic acid (2R,3S,4R,5R)-2-azido-3,4-bis-benzoyloxy-5-(4-imidazol-1-yl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester with an assay of 99.3% (area).

後処理

  1. temperatureThe mixture was then cooled to 15° C.
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with MeTHF (1×30 ml)
  4. customFrom the organic layer MeTHF was completely removed by distillation
  5. additionWater (50 ml) and methylene chloride (100 ml) were added
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with methylene chloride (1×100 ml)
  8. filtrationThe organic layer was filtered
  9. customthe solvent was evaporated
  10. dry with materialthe residue (34.2 g) dried in vacuo (<30 mbar) at 40° C. for 16 hours

出典と根拠

ORDレコード
ord-f817ff1ca9a34952a1ab2f899608c182
出典データセット
uspto-grants-2009_12
特許番号
US07632940B2

反応ノート

読み込み中…