Acetic Acid → 5'-O-(tert-Butydimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

HRID 1052873ノート

反応式

HRID 1052873 の反応式
[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[OH:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(=O)C.C(OC(=O)C)(=O)C.[CH3:45][S:46]([CH3:48])=O>>[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:30])([F:31])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[O:33][CH2:45][S:46][CH3:48])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

参加物

5

反応物 4

HCID 176Acetic AcidHCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 866642615'-O-(tert-butydimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

生成物 1

HCID 873394095'-O-(tert-Butydimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine収率 89%

実験手順

To a solution of (2) (1.84 g, 3.7 mmol) in dry DMSO (7 ml) was added acetic acid (3.2 ml) and acetic anhydride (10.2 ml). The mixture was stirred for 2 days at room temperature, before it was quenched with sat. aq. NaHCO3. EtOAc (50 ml) was added and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with sat. aq. NaHCO3 solution and dried (MgSO4). After removing the solvent under reduced pressure, the product (3) was purified by chromatography on silica (EtOAc:petroleum ether 8:2) yielding a clear sticky oil (1.83 g, 89%). 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.79 (s, 9H, tBu), 1.96-2.06 (m, 1H, H-2′), 1.99 (s, 3H, SCH3), 2.20-2.26 (m, 1H, H-2′), 3.63-3.74 (m, 2H, H-5′), 3.92-3.95 (m, 1H, H-4′), 4.11-4.13 (m, 2H, CH2), 4.28-4.30 (m, 1H, H-3′), 4.59 (br s, 2H, CH2), 5.97 (t, J=6.9 Hz, 1H, H-1′), 7.85 (s, 1H, H-6), 9.95 (t, J=5.3 Hz, 1H, NH), 11.64 (s, 1H, NH). Mass (−ve electrospray) calcd for C22H32F3N3O6SSi 551.17. found 550.

後処理

  1. customwas quenched with sat. aq. NaHCO3
  2. additionEtOAc (50 ml) was added
  3. extractionthe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 solution
  5. dry with materialdried (MgSO4)
  6. customAfter removing the solvent under reduced pressure
  7. customthe product (3) was purified by chromatography on silica (EtOAc:petroleum ether 8:2)

出典と根拠

ORDレコード
ord-25c7943682514ae18da65016e056b9a9
出典データセット
uspto-grants-2016_07
特許番号
US09388464B2

反応ノート

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