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Hexamethyldisilazane → 2',3'-di-O-methoxycarbonyl-5'-deoxy-5-fluorocytidine

HRID 420836
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HRID 420836 반응식
[F:1][C:2]1[C:3]([NH2:9])=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.C[Si](C)(C)N[Si](C)(C)C.COC(O[CH:24]1[O:38][C@H:37]([CH3:39])[C@@H:31]([O:32][C:33]([O:35][CH3:36])=[O:34])[C@H:25]1[O:26][C:27]([O:29][CH3:30])=[O:28])=O.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(=O)([O-])O.[Na+]>S([O-])([O-])(=O)=O.[NH4+].[NH4+].ClCCl.O.C(#N)C>[CH3:30][O:29][C:27]([O:26][C@@H:25]1[C@H:31]([O:32][C:33]([O:35][CH3:36])=[O:34])[C@@H:37]([CH3:39])[O:38][C@H:24]1[N:6]1[CH:7]=[C:2]([F:1])[C:3]([NH2:9])=[N:4][C:5]1=[O:8])=[O:28]
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참가 물질

10

반응물 5

HCID 13838HexamethyldisilazaneHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 666573491,2,3-tri-O-methoxycarbonyl-5-deoxy-D-ribofuranoseHCID 178509021HCID 178509021, 화합물

생성물 1

HCID 666574402',3'-di-O-methoxycarbonyl-5'-deoxy-5-fluorocytidine
수율 110.1%

시약·촉매·용매 4

HCID 6097028Ammonium Sulfate촉매HCID 962Water용매HCID 6342Acetonitrile용매3회HCID 6344Dichloromethane용매

실험 절차

11.6 g (0.090 mole) of 5-fluorocytosine, 19 ml of hexamethyldisilazane and 24 ml of acetonitrile were mixed, and 0.2 g of ammonium sulfate was added to the mixture, which was refluxed for 1 hr. After cooling the reaction mixture to room temperature, 72 ml of acetonitrile was added thereto, followed by subjecting the resulting mixture to distillation to remove about 60 ml of the solvent. The resulting solution was cooled to room temperature, mixed with 27.7 g (0.090 mole) of the compound obtained in Example 1 and 72 ml of acetonitrile, and the resulting mixture was cooled to 20° C. After adding 16.3 ml (0.090 mole) of trimethylsilyl trifluoromethanesulfonate dropwise thereto at 25° C., the reaction mixture was stirred at room temperature overnight, cooled to 10° C., mixed with 45.4 g of sodium hydrogen carbonate, and stirred for 30 min. 9.8 g of water and 72 ml of dichloromethane were added dropwise thereto, the resulting solution was stirred for 2 hrs, filtered, and the isolated solid was washed with 72 ml of dichloromethane. The filtrate was washed with 120 ml of 4% sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and concentrated under a reduced pressure, to obtain 35.8 g of the title compound.

후처리

  1. temperaturewas refluxed for 1 hr
  2. distillationto distillation
  3. customto remove about 60 ml of the solvent
  4. temperatureThe resulting solution was cooled to room temperature
  5. temperaturethe resulting mixture was cooled to 20° C
  6. temperaturecooled to 10° C.
  7. stirringstirred for 30 min
  8. stirringthe resulting solution was stirred for 2 hrs
  9. filtrationfiltered
  10. washthe isolated solid was washed with 72 ml of dichloromethane
  11. washThe filtrate was washed with 120 ml of 4% sodium bicarbonate
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under a reduced pressure

출처 및 근거

ORD 기록
ord-61b075de1b48453bb52605b985ee7c71
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08097706B2

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