Methane → Fludarabine

HRID 2057486Notes

Reaction equation

HRID 2057486 reaction equation
C([O:8][C@H:9]1[C@H:13]([O:14]CC2C=CC=CC=2)[C@@H:12]([CH2:22][O:23]CC2C=CC=CC=2)[O:11][C@H:10]1[N:31]1[CH:39]=[N:38][C:37]2[C:32]1=[N:33][C:34]([F:41])=[N:35][C:36]=2[NH2:40])C1C=CC=CC=1.C(=O)(O)[O-].[Na+].C>C(Cl)Cl.C(O)C>[C@@H:10]1([N:31]2[CH:39]=[N:38][C:37]3[C:32]2=[N:33][C:34]([F:41])=[N:35][C:36]=3[NH2:40])[O:11][C@H:12]([CH2:22][OH:23])[C@@H:13]([OH:14])[C@@H:9]1[OH:8]

Participants

6

Reactant 3

HCID 297MethaneHCID 516892Sodium Bicarbonate2×HCID 109627089-(2,3,5-Tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine

Product 1

HCID 657237Fludarabine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

Boron trichloride gas was bubbled in methylene chloride (610 ml.) at 0° in a 2-l., 3-necked flask equipped with a thermometer, magnetic stirrer, and addition funnel and the stirred solution then cooled to -72° (dry ice-acetone) before the dropwise addition (1 hour) of a cold solution of 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2-fluoroadenine (6, 7.0 g., 12.5 mmoles) in methylene chloride (70 ml.). After a total reaction time of 2.75 hours, the cooling bath was removed and the solvent and gas removed in vacuo. The residue was dissolved in cold methylene chloride (40 ml.) and the solution evaporated to dryness (6 times) or until a solid white residue was obtained, before adding 450 ml. of cold 5% sodium bicarbonate followed by solid sodium bicarbonate to adjust the pH to 6-7. The mixture was diluted with ethanol, heated to boiling, treated with charcoal, filtered through Celite, and then allowed to stand at room temperature overnight. It was then chilled and the solid collected by filtration, washed with cold water and then ether, and dried in vacuo; yield 3.23 g. (91%); m.p. 259°-260°; homogeneous according to tlc (19:1) and hplc (23 water:2 acetonitrile); nmr: 3.7 (m, H4' and 2H5'), 4.15 (m, H2' and H3'), 5.1 (t, 5'--OH), 5.55 and 5.65 (2d, 2'-13 OH and 3'--OH), 6.14 (d, J'2' 3 Hz, H1'), 7.8 (broad s, NH2), 8.2 (s, H8); uv: pH 1-262 (13.2); pH 7, 13-261 (15.3).

Workup

  1. customBoron trichloride gas was bubbled in methylene chloride (610 ml.) at 0° in a 2-l
  2. custom, 3-necked flask equipped with a thermometer, magnetic stirrer, and addition funnel
  3. temperaturethe stirred solution then cooled to -72° (dry ice-acetone)
  4. customAfter a total reaction time of 2.75 hours, the cooling bath was removed
  5. customthe solvent and gas removed in vacuo
  6. dissolutionThe residue was dissolved in cold methylene chloride (40 ml.)
  7. customthe solution evaporated to dryness (6 times) or until a solid white residue
  8. customwas obtained
  9. additionbefore adding 450 ml
  10. temperatureheated to boiling
  11. filtrationfiltered through Celite
  12. temperatureIt was then chilled
  13. filtrationthe solid collected by filtration
  14. washwashed with cold water
  15. dry with materialether, and dried in vacuo

Sources & evidence

ORD record
ord-a4dfe1e3a97744aa960fc11051dc32ea
Source dataset
uspto-grants-1980_07
Patent number
US04210745

Reaction notes

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