Hexamethyldisilazane → 3'-Deoxy-5'-O-(4-methoxytrityl)-3'-methyl-2'-O-(2-methoxyethyl)-5-methyluridine

HRID 2212899

反応式

HRID 2212899 の反応式
[PH2](=O)[O-].[NH4+].C[Si](C)(C)N[Si](C)(C)C.[CH3:14][O:15][C:16]1[CH:57]=[CH:56][C:19]([C:20]([O:33][CH2:34][C@H:35]2[O:39][C@@H:38]([N:40]3[CH:47]=[C:46]([CH3:48])[C:44](=[O:45])[NH:43][C:41]3=[O:42])[C@H:37]([O:49][CH2:50][CH2:51][O:52][CH3:53])[C@@H:36]2[CH2:54]I)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C>ClCCl.C1COCC1.CO.CCN(CC)CC>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([O:33][CH2:34][C@H:35]2[O:39][C@@H:38]([N:40]3[CH:47]=[C:46]([CH3:48])[C:44](=[O:45])[NH:43][C:41]3=[O:42])[C@H:37]([O:49][CH2:50][CH2:51][O:52][CH3:53])[C@@H:36]2[CH3:54])([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:56][CH:57]=1

参加物

7

反応物 4

HCID 13838HexamethyldisilazaneHCID 81531DiisopropylethylamineHCID 235183323'-Deoxy-5'-O-(4-methoxytrityl)-3'-(iodomethyl)-2'-O-(2-methoxyethyl)-5-methyluridineHCID 178418291HCID 178418291、化合物

生成物 1

HCID 235183333'-Deoxy-5'-O-(4-methoxytrityl)-3'-methyl-2'-O-(2-methoxyethyl)-5-methyluridine収率 58.9%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 67203757THF MeOH NEt3溶媒

反応条件

温度
105 °C

実験手順

A mixture of ammonium phosphinate (410 mg, 5.1 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (1.18 mL, 0.90 g, 5.59 mmol) was heated at 100-110° C. for 2 h under nitrogen atmosphere with condenser. The intermediate BTSP(bis[trimethylsilyl]phosphinate) was cooled to 0° C. and 5 mL of dichloromethane was injected. To this mixture was injected a solution of 3′-deoxy-5′-O-(4-methoxytrityl)-3′-(iodomethyl)-2′-O-(2-methoxyethyl)-5-methyluridine (0.78 g, 1.1 mmol) and diisopropylethylamine (0.39 mL, 287 mg, 2.23 mmol) in 7 mL of dichloromethane. After the reaction mixture was stirred at rt overnight, a mixture of THF-MeOH-NEt3 (3/6/0.3 mL) was added and continued to stir for 1 h. The reaction mixture was filtered through a pad of celite and washed with dichloromethane. The solvent was evaporated and the residue was purified by flash chromatography on a silica gel column using 2:1, 1:1, and then 1:2 hexanes-EtOAc as eluent providing 380 mg of the title compound.

後処理

  1. additionwas added
  2. stirringto stir for 1 h
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. washwashed with dichloromethane
  5. customThe solvent was evaporated
  6. customthe residue was purified by flash chromatography on a silica gel column

出典と根拠

ORDレコード
ord-928e3d1733b34483a2360f813dce3fae
出典データセット
uspto-grants-2006_09
特許番号
US07105499B2

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