Dichloromethane → 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine

HRID 1910406Notes

Reaction equation

HRID 1910406 reaction equation
[F:1][C:2]1[C:3]([NH2:9])=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.C(Cl)Cl.C(O[C@@H:17]1[O:29][C@H:28]([CH3:30])[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:18]1[O:19][C:20](=[O:22])[CH3:21])(=O)C.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.O>[C:20]([O:19][C@@H:18]1[C@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@@H:28]([CH3:30])[O:29][C@H:17]1[N:6]1[CH:7]=[C:2]([F:1])[C:3]([NH2:9])=[N:4][C:5]1=[O:8])(=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium Bicarbonate2×HCID 11821332beta-D-Ribofuranose, 5-deoxy-, 1,2,3-triacetateHCID 178509021HCID 178509021, compound

Product 1

HCID 118096352',3'-di-O-acetyl-5'-deoxy-5-fluorocytidineYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

5-Fluorocytosine (2.42 g, 18.8 mmol) was suspended in toluene (10 ml) and hexyamethyl-disilazane (3.03 g, 18.8 mmol). The mixture was heated at 100° C. overnight. After concentrating the reaction mixture under reduced pressure, methylene chloride (30 ml) and 5-deoxy-1,2,3-tri-O-Acetyl-β-D-ribofuranoside (4) (5.16 g, 18.8 mmol) were added to the residue. Then, anhydrous stannic chloride (4.90 g, 18.8 mmol) was added dropwise to the ice-cooled reaction mixture over a period of 20 min. After stirring the mixture at room temperature for an additional 2 h, sodium bicarbonate (10 g) was added, followed by the dropwise addition of water (20 ml). After stirring the resulting mixture at room temperature overnight, 4% sodium bicarbonate solution was poured into the reaction mixture and stirred for additional 1 h. The mixture was then extracted with water-methylene chloride. The organic layer was collected, dried with Na2SO4, the solvent was removed under reduced pressure to give brown syrup. The residue was then partially purified by silica gel chromatography using CH2Cl2:MeOH (5:1) as an eluent to yield crude target compound (5) (4.455 g, 13.5 mmol, 72%). 1H NMR in DMSO-d6: δ1.34 (d, 3H, J=6.4 Hz, H-5), 2.05, 2.06 (2s, each 3H, OMe), 4.14 (q, 1H, J=5.0 Hz, H-4), 5.10 (t, 1H, J=6.4 Hz, H-2), 5.43 (dd, 1H, J=6.31 Hz, H-3), 5.77 (dd, 1H, J=1.0 Hz, H-1), 7.71 (br s, 1H, N—CH═C—F), 7.97 (br s, 1H, NH), 8.02 (d, 1H, J=7.0 Hz, NH).

Workup

  1. additionwere added to the residue
  2. temperaturecooled
  3. customreaction mixture over a period of 20 min
  4. additionwas poured into the reaction mixture
  5. stirringstirred for additional 1 h
  6. extractionThe mixture was then extracted with water-methylene chloride
  7. customThe organic layer was collected
  8. dry with materialdried with Na2SO4
  9. customthe solvent was removed under reduced pressure
  10. customto give brown syrup
  11. customThe residue was then partially purified by silica gel chromatography

Sources & evidence

ORD record
ord-8f0c454e448e4bd6a4947edf2a1b3774
Source dataset
uspto-grants-2013_12
Patent number
US08603999B2

Reaction notes

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