Tetrafluoroboric acid → HCID 44323403, compound

HRID 1647517Notes

Reaction equation

HRID 1647517 reaction equation
C([O:4][C@@H:5]1[C@H:9]([O:10]C(=O)C)[C@@H:8]([CH2:14][O:15]C(=O)C)[O:7][C@H:6]1[N:19]1[C:34]2[N:33]=[C:32](N)[N:31]=[C:23]([NH:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[C:22]=2[N:21]=[CH:20]1)(=O)C.[F:36][B-](F)(F)F.[H+].N([O-])=O.[Na+]>C1COCC1>[F:36][C:32]1[N:31]=[C:23]([NH:24][N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[C:22]2[N:21]=[CH:20][N:19]([C:34]=2[N:33]=1)[C@@H:6]1[O:7][C@H:8]([CH2:14][OH:15])[C@@H:9]([OH:10])[C@H:5]1[OH:4]

Participants

5

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 22854551HCID 22854551, compoundHCID 23668193Sodium Nitrite2×

Product 1

HCID 44323403HCID 44323403, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The above 2',3',5'-tri-O-acetyl-N-(1-piperidinyl)adenosine (1.33 g, 2.7 mmol) was dissolved in THF (50 ml) and the temperature of the solution was held between -10° C. and -20° C. Fluoroboric acid (48%, 100 ml) was added followed by an aqueous solution of sodium nitrite (0.75 g/ml, 1.5 ml). Addition of three identical amounts of sodium nitrite was continued at 0.3 hour intervals, after which TLC investigation (on a neutralised sample) indicated that the starting material was consumed [rf 0.47 (SiO2, ethyl acetate/methanol (90/10))]. The pH of the reaction mixture was adjusted to ca. 6 with 50% sodium hydroxide solution with cooling to below 0° C. and the now red reaction mixture was diluted with water (250 ml). The solution was extracted with chloroform (2×100 ml) and the combined extracts were dried (MgSO4). The residue on evaporation (containing 2',3',5'-tri-O-acetyl-2-fluoro-N-(1-piperidinyl)adenosine was treated with methanolic ammonia (150 ml) (previously saturated at -10° C.) and stirred at room temperature for 72 hours. The reaction mixture was evaporated and the resultant residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (0-10%) to provide the title compound (0.093 g) as a white solid, after washing with ethyl acetate. M.p. 197°-199° C.; 1H NMR (400 MHz, Me2SO-d6) δ3.57, 3.65 (2H, ABX, H-5'a and H-5'b), 3.92 (1H, q, H-4'), 4.12 (1H, m, H-3'), 4.50 (1H, q, H-2'), 5.80 (1H, d, H-1'), 8.35 (1H, s, H-8). HPLC retention time 10.12 (gradient elution, 5-25% acetonitrile/0.1M pH 3.3 ammonium sulphate buffer: 214 nm detector): 100% purity.

Workup

  1. customwas held between -10° C. and -20° C
  2. customwas consumed [rf 0.47 (SiO2, ethyl acetate/methanol (90/10))]
  3. temperaturewith cooling to below 0° C.
  4. additionthe now red reaction mixture was diluted with water (250 ml)
  5. extractionThe solution was extracted with chloroform (2×100 ml)
  6. dry with materialthe combined extracts were dried (MgSO4)
  7. customThe residue on evaporation (
  8. additioncontaining 2',3',5'-tri-O-acetyl-2-fluoro-N-(1-piperidinyl)adenosine
  9. additionwas treated with methanolic ammonia (150 ml) (previously saturated at -10° C.) and
  10. customThe reaction mixture was evaporated
  11. customthe resultant residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (0-10%)

Sources & evidence

ORD record
ord-0fd0a9612a58497a9ae45dc0aaab3141
Source dataset
uspto-grants-1995_07
Patent number
US05432164

Reaction notes

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