Acetic Acid → 4-N-benzoyl-5-methylseleno-5'-O-(4,4-dimethoxytrityl)-2'-deoxycytidine

HRID 2406287ノート

反応式

HRID 2406287 の反応式
[C:1]([NH:9][C:10]1[C:53]([Se:54][CH3:55])=[CH:52][N:13]([C@@H:14]2[O:44][C@H:18]([CH2:19][O:20][C:21]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:22]3[CH:27]=[CH:26][C:25]([O:30][CH3:31])([O:28][CH3:29])[CH2:24][CH:23]=3)[C@@:16]([Si](C(C)(C)C)(C)C)([OH:17])[CH2:15]2)[C:12](=[O:56])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.CO>ClCCl>[C:1]([NH:9][C:10]1[C:53]([Se:54][CH3:55])=[CH:52][N:13]([C@@H:14]2[O:44][C@H:18]([CH2:19][O:20][C:21]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])([O:30][CH3:31])[CH2:26][CH:27]=3)[C@@H:16]([OH:17])[CH2:15]2)[C:12](=[O:56])[N: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 3

HCID 176Acetic AcidHCID 887MethanolHCID 1317317744-N-benzoyl-5-methylseleno-3'-t-butyldimethylsilyl-5'-O-(4,4-dimethoxytrityl)-2'-deoxycytidine2 回

生成物 1

HCID 866632984-N-benzoyl-5-methylseleno-5'-O-(4,4-dimethoxytrityl)-2'-deoxycytidine収率 91%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

4-N-benzoyl-5-methylseleno-3′-t-butyldimethylsilyl-5′-O-(4,4-dimethoxytrityl)-2′-deoxycytidine (compound 3) 280 mg (MW 8553, 0.33 mmol) was placed in a flask and dried under high vacuum before it was dissolved in anhydrous THF. The solution was placed in an ice-water bath under dry argon tetra-Butylammonium fluoride 0.44 ml (1M solution in THY, 1.2 eq.) and acetic acid 0.03 ml (1.2 eq.) were injected dropwise simultaneously to make solution pH keep about 7. The reaction mixture was stirred for overnight before it was completed (monitored on TLC, 3% methanol in dichloromethane, Rf=0.35). The crude product was extracted by EtOAc and NaCl solution (sat.) three times, and the combined organic layer was dried over anhydrous MgSO4, followed by filtration and solvent evaporation. The residue was purified on a silica gel column (equilibrated with CH2Cl2) and eluted with a methanol/dichloromethane gradient (0.5-5%) to afford the desired product compound 4225 mg. (yield=91%). 1H-NMR (400 MHz, DMSO) δ: 2.04 (s, 3H, SeCH3), 2.21-2.26 and 2.69-2.76 (2×m, 2H, H-2′), 3.34-3.47 (2×m, 2H, H-5′), 3.79 (s, 6H, 2×OMe), 4.15-4.17 (m, 1H, H-3′), 4.46-4.48 (m, 1H, H-4′), 6.14-6.17 (t, J=6.4 Hz, 1H, H-1′), 6.84-7.79 (m, 18H, arom-H), 8.48 (s, 1H, H-6). 13C NMR (100 MHz, DMSO) δ: 11.02 (SeCH3), 41.99 (C-2′), 55.27 (OMe), 63.11 (C-5′), 72.41 (C-3′), 86.67 (C-4′), 86.94 (arom-C), 87.87 (C-1′), 102.39 (C-5), 113.31 (arom-C), 127.07 (arom-C), 128.04 (arom-C), 128.07 (arom-C), 128.29 (arom-C), 129.68 (arom-C), 129.45 (arom-C), 130.00 (arom-C), 130.92 (arom-C), 132.70 (arom-C), 134.22 (arom-C), 135.47 (NHCO), 144.41 (arom-C), 144.32 (C-2), 150.83 (C-6), 158.69 (C-4), 172.28 (arom-C).

後処理

  1. customdried under high vacuum before it
  2. dissolutionwas dissolved in anhydrous THF
  3. customThe solution was placed in an ice-water bath under dry argon tetra-Butylammonium fluoride 0.44 ml (1M solution in THY, 1.2 eq.)
  4. extractionThe crude product was extracted by EtOAc and NaCl solution (sat.) three times
  5. dry with materialthe combined organic layer was dried over anhydrous MgSO4
  6. filtrationfollowed by filtration and solvent evaporation
  7. customThe residue was purified on a silica gel column (equilibrated with CH2Cl2)
  8. washeluted with a methanol/dichloromethane gradient (0.5-5%)

出典と根拠

ORDレコード
ord-edd94036a9f44c7bb26fa9f93d2cb695
出典データセット
uspto-grants-2014_08
特許番号
US08809357B2

反応ノート

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