Tert-Butyl nitrite → 6-azido-2-fluoro-7H-purine

HRID 1646665Notes

Reaction equation

HRID 1646665 reaction equation
N[C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([N:11]=[N+:12]=[N-:13])[N:3]=1.[H+].[B-](F)(F)(F)[F:16].C(ON=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(OCC)(=O)C.O>[N:11]([C:4]1[N:3]=[C:2]([F:16])[N:10]=[C:9]2[C:5]=1[NH:6][CH:7]=[N:8]2)=[N+:12]=[N-:13]

Participants

8

Reactant 4

HCID 10906Tert-Butyl nitriteHCID 11430Potassium CarbonateHCID 28118Tetrafluoroboric acidHCID 197576806-Azido-7H-purin-2-amine

Product 1

HCID 198012676-azido-2-fluoro-7H-purine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-amino-6-azidopurine (13.0 gm, 73.6 mmol) in tetrahydrofuran (THF, 163 mL), and 48% aqueous HBF4 (42.24 mL) was cooled in a bath at -20° C. A solution of t-butylnitrite (12.65 mL) in THF (10 mL) was added over a 5 minute period. The bath was replaced with an ice-water bath for 30 minutes and then with a bath at 50° C. for 15 minutes. The mixture was then poured over ice (600 g), and water (200 mL) was added. The suspension was neutralized (pH 6-7) with saturated potassium carbonate (K2CO3), and ethyl acetate was added. The resulting solid potassium fluoborate (KBF4) was collected by filtration and washed thoroughly with ethyl acetate. The aqueous layer was washed repeatedly with ethyl acetate and the combined ethyl acetate extracts were washed sequentially with water (500 mL) and saturated sodium chloride (NaCl) (250 mL) and dried over magnesium sulfate (MgSO4) along with decolorizing carbon. The ethyl acetate was then filtered through celite and concentrated in vacuo to afford 9.36 g of the title compound. mp 190°-195° C. (d) (from ethyl acetate/pet. ether; The decomposition or melting point of this material varies from sample to sample); IR (KBr) 2240, 2200, 1620, 1595, 1565 cm-1 ; MS (EI+, m/z) 179(M+, 55%), 151 ((M-N2)+, 100%); 1H NMR (DMSO-d6, 360 MHz) δ8.53 (s, 1H), 13.8 (bs, 1H); 13C NMR (DMSO-d6, 90 MHz) 120 (very broad), 145.4 (broad), 152.2 (broad), 156 (very broad), 157.0 (d, JCF =210 Hz) ppm; UV (MeOH) λmax, 250, 286 nm.

Workup

  1. waitwith a bath at 50° C. for 15 minutes
  2. additionwas added
  3. additionwas added
  4. filtrationThe resulting solid potassium fluoborate (KBF4) was collected by filtration
  5. washwashed thoroughly with ethyl acetate
  6. washThe aqueous layer was washed repeatedly with ethyl acetate
  7. washthe combined ethyl acetate extracts were washed sequentially with water (500 mL) and saturated sodium chloride (NaCl) (250 mL)
  8. dry with materialdried over magnesium sulfate (MgSO4) along with decolorizing carbon
  9. filtrationThe ethyl acetate was then filtered through celite and
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e37a905784da42c09e6fa3d1f0ce1674
Source dataset
uspto-grants-1993_01
Patent number
US05180824

Reaction notes

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