Sodium Hydroxide → 9-(2,3,5-Tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine

HRID 2057485Notes

Reaction equation

HRID 2057485 reaction equation
N[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:31][C@H:30]([CH2:32][O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@@H:21]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@@H:12]2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:4]([NH2:41])[N:3]=1.[H+].[B-](F)(F)(F)[F:44].N([O-])=O.[Na+].NC1N=C2C(NC=N2)=C(N)N=1.[OH-].[Na+]>O1CCCC1>[CH2:14]([O:13][C@H:12]1[C@H:21]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:30]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:31][C@H:11]1[N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([F:44])=[N:3][C:4]=2[NH2:41])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 28118Tetrafluoroboric acid2×HCID 309762,6-DiaminopurineHCID 108969412-Amino-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)adenineHCID 23668193Sodium Nitrite2×

Product 1

HCID 109627089-(2,3,5-Tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)adenine (5, 15.0 g., 27.1 mmoles) in a mixture of 500 ml. tetrahydrofuran and 1 l. of 48% fluoboric acid at -10° in a 4-l. beaker equipped with a mechanical stirrer was added dropwise in 20 minutes a saturated aqueous solution of sodium nitrite (7.5 g., 108 mmoles). The addition of sodium nitrite was repeated three times after which none of the 2-aminoadenine remained (tlc). The fluorboric acid was neutralized to pH 6 with 505% sodium hydroxide keeping the temperature between -40° and 0°. The solution was extracted four times with chloroform (300 ml., 250 ml., and two 200-ml. portions). The chloroform extract was washed with saturated sodium chloride solution and then dried over magnesium sulfate before it was evaporated to dryness in vacuo. The residual oil was dissolved in a liter of ethanolic ammonia (saturated at 0°), and the solution was allowed to stand for 4 days at 4° before it was evaporated to dryness. The residue was recrystallized from ethanol; yield 5.5 g. Additional material was recovered from the filtrate by recrystallization and the final filtrate was evaporated to dryness, diluted with 50 ml. of 1 N hydrochloric acid, stirred on a steam bath for 30 minutes, cooled, and the aqueous portion decanted. A chloroform solution of the residue was washed with saturated sodium bicarbonate, then water, and dried over magnesium sulfate before evaporation in vacuo. The residue was recrystallized from ethanol; total yield of 6, 7.2 g. (48%); m.p. 155°-157°. This material was essentially homogeneous according to tlc (19:1) and hplc [2 aqueous pentanesulfonic acid (0.005 M):3 acetonitrile-3% acetic acid].

Workup

  1. customat -10°
  2. custombeaker equipped with a mechanical stirrer
  3. customthe temperature between -40° and 0°
  4. extractionThe solution was extracted four times with chloroform (300 ml., 250 ml., and two 200-ml. portions)
  5. extractionThe chloroform extract
  6. washwas washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate before it
  8. customwas evaporated to dryness in vacuo
  9. dissolutionThe residual oil was dissolved in a liter of ethanolic ammonia (saturated at 0°)
  10. customwas evaporated to dryness
  11. customThe residue was recrystallized from ethanol
  12. customAdditional material was recovered from the filtrate by recrystallization
  13. customthe final filtrate was evaporated to dryness
  14. additiondiluted with 50 ml
  15. temperaturecooled
  16. customthe aqueous portion decanted
  17. washA chloroform solution of the residue was washed with saturated sodium bicarbonate
  18. dry with materialwater, and dried over magnesium sulfate before evaporation in vacuo
  19. customThe residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-050ced0cdf2f4780bb0f06b3b6be6923
Source dataset
uspto-grants-1980_07
Patent number
US04210745

Reaction notes

Loading…