Tert-Butyl nitrite → 2-Fluoroadenosine

HRID 1939615Notes

Reaction equation

HRID 1939615 reaction equation
N[C:2]1[N:3]=[C:4]([NH2:20])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11].N(OC(C)(C)C)=O.[OH-].[Ca+2].[OH-].C1C=CN=CC=1.[FH:37]>O.N>[F:37][C:2]1[N:3]=[C:4]([NH2:20])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11]

Participants

7

Reactant 4

HCID 10906Tert-Butyl nitriteHCID 64774Pyridine, hydrofluoride (1:1)HCID 722002-AminoadenosineHCID 6093208Calcium Hydroxide

Product 1

HCID 89752-FluoroadenosineYield 91%

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 962WaterSolvent

Conditions

Temperature
-30 °C

Procedure

0.282 g (1 mmol) of 2-aminoadenosine is suspended in a mixture of 7 ml of 50% HF-pyridine and 0.35 ml of H2O at -30° C. and within 30 minutes, 1.2 ml (~9 mol) of tert-butyl nitrite is instilled slowly with vigorous stirring at -30° C. After another 30 minutes at -25°→-30° C., the reaction mixture is instilled slowly in 120 ml of 33% aqueous ammonia at -10° C. with stirring and stirred for 1 hour at 0° C. After adding 7 g of solid calcium hydroxide, it is stirred for another 15 minutes at 0° C., filtered and washed with 40 ml of H2O. The light yellow filtrate is carefully concentrated by evaporation at about 25° C.-30° C. to about 15 ml and CO2 is introduced. After filtering off the small amount of precipitate and after washing the precipitate with 10 ml of H2O, the filtrate is concentrated by evaporation at a 10 mm vacuum. The yellowish-brown residue (0.39 g) is dissolved in 15 ml of methanol-H2O (1:1), mixed with 10 g of silica gel (40% H2O) and evaporated at a 10 mm vacuum. After feeding dry silica gel containing the substance on a column of 15 g of silica gel (40% H2O), which was taken up with isopropanol, elution with about 300 ml of isopropanol yields 0.261 g (~91%) of crude 2-fluoroadenosine, which still contains a little 2-aminoadenosine as well as isoguanosine.

Workup

  1. stirringwith stirring
  2. stirringstirred for 1 hour at 0° C
  3. stirringis stirred for another 15 minutes at 0° C.
  4. filtrationfiltered
  5. washwashed with 40 ml of H2O
  6. concentrationThe light yellow filtrate is carefully concentrated by evaporation at about 25° C.-30° C. to about 15 ml and CO2
  7. additionis introduced
  8. filtrationAfter filtering off the small amount of precipitate
  9. washafter washing the precipitate with 10 ml of H2O
  10. concentrationthe filtrate is concentrated by evaporation at a 10 mm vacuum
  11. dissolutionThe yellowish-brown residue (0.39 g) is dissolved in 15 ml of methanol-H2O (1:1)
  12. additionmixed with 10 g of silica gel (40% H2O)
  13. customevaporated at a 10 mm vacuum
  14. washwas taken up with isopropanol, elution with about 300 ml of isopropanol

Sources & evidence

ORD record
ord-6506746f7f934122807810ca131dd935
Source dataset
uspto-grants-1997_12
Patent number
US05696255

Reaction notes

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