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

HRID 1270241

反応式

HRID 1270241 の反応式
[PH2](=O)[O-].[NH4+].C[Si](C)(C)N[Si](C)(C)C.C[Si](P([Si](C)(C)C)(=O)[O-])(C)C.[CH3:25][O:26][C:27]1[CH:68]=[CH:67][C:30]([C:31]([O:44][CH2:45][C@H:46]2[O:50][C@@H:49]([N:51]3[CH:58]=[C:57]([CH3:59])[C:55](=[O:56])[NH:54][C:52]3=[O:53])[C@H:48]([O:60][CH2:61][CH2:62][O:63][CH3:64])[C@@H:47]2[CH2:65]I)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:29][CH:28]=1.C(N(C(C)C)CC)(C)C>ClCCl.C1COCC1.CO.CCN(CC)CC>[CH3:25][O:26][C:27]1[CH:28]=[CH:29][C:30]([C:31]([O:44][CH2:45][C@H:46]2[O:50][C@@H:49]([N:51]3[CH:58]=[C:57]([CH3:59])[C:55](=[O:56])[NH:54][C:52]3=[O:53])[C@H:48]([O:60][CH2:61][CH2:62][O:63][CH3:64])[C@@H:47]2[CH3:65])([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:67][CH:68]=1

参加物

8

反応物 5

HCID 13838HexamethyldisilazaneHCID 81531DiisopropylethylamineHCID 18448993Bis(trimethylsilyl)phosphinateHCID 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

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. temperaturewas heated at 100–110° C. for 2 h under nitrogen atmosphere with condenser
  2. additionwas added
  3. stirringto stir for 1 h
  4. filtrationThe reaction mixture was filtered through a pad of celite
  5. washwashed with dichloromethane
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash chromatography on a silica gel column

出典と根拠

ORDレコード
ord-2116b77b0b1444708d7343bc33bace0c
出典データセット
uspto-grants-2007_04
特許番号
US07202224B2

関連ノート

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