Dichloromethane → 3-Pyridinol, 6-bromo-, 3-acetate

HRID 2185763Notes

Reaction equation

HRID 2185763 reaction equation
B(F)(F)F.[CH3:5][CH2:6][O:7][CH2:8][CH3:9].NC1[CH:12]=[N:13][C:14]([Br:17])=[CH:15]C=1.N(OC(C)(C)C)=[O:19].C(Cl)Cl>C(COC)OC.CCCCC>[C:6]([O:7][C:8]1[CH:12]=[N:13][C:14]([Br:17])=[CH:15][CH:9]=1)(=[O:19])[CH3:5]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 6428116-Bromopyridin-3-amine

Product 1

HCID 224515843-Pyridinol, 6-bromo-, 3-acetateYield 60.5%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To 25.6 mL of boron trifluoride etherate (208 mmol, Aldrich) cooled to −15° C. under N2 was added 18 g (104 mmol) of 3-amino-6-bromopyridine (from Step 123a above) dissolved in 35 mL of dimethoxyethane. Then t-Butyl nitrite (14.7 mL, 125 mmol, Aldrich) was added at a rate which kept the temperature below 0° C. Dimethoxyethane (65 mL) and methylene chloride (60 mL) were then added to aid stirring. After 10 minutes at −10° C. the mixture was allowed to warm to 5° C. and stirred for 30 minutes. Pentane (400 mL) was then added to the reaction mixture, the solid was collected by suction filtration, washed with cold ether, air dried, and dissolved in 125 mL of acetic anhydride. The resulting solution was heated to 100° C.±5° C. for 1 hour. The solvent was removed in vacuo, and the residue was suspended in saturated aqueous Na2CO3, and extracted with ethyl ether. The ether solution was dried over MgSO4, the solvent was removed in vacuo, and the residue was chromatographed on silica gel, eluting with 100:0 to 60:40 hexane:ethyl acetate to give 13.6 g of the title compound: 1H NMR (CDCl3 300 MHz) δ8.20 (m, 1H).7.51 (d, J=8.5 Hz 1H),7.38 (dd, J 2.9, 7.5 Hz, 1H), 2.35 (s, 3H). MS (CI/NH3) m/e: 216 (M+H)+, 233 (M+NH4)+.

Workup

  1. customthe temperature below 0° C
  2. stirringstirred for 30 minutes
  3. filtrationthe solid was collected by suction filtration
  4. washwashed with cold ether, air
  5. customdried
  6. dissolutiondissolved in 125 mL of acetic anhydride
  7. temperatureThe resulting solution was heated to 100° C.±5° C. for 1 hour
  8. customThe solvent was removed in vacuo
  9. extractionextracted with ethyl ether
  10. dry with materialThe ether solution was dried over MgSO4
  11. customthe solvent was removed in vacuo
  12. customthe residue was chromatographed on silica gel
  13. washeluting with 100:0 to 60:40 hexane

Sources & evidence

ORD record
ord-ef5937b2890d48e0b20ab26adde56df1
Source dataset
uspto-grants-2002_06
Patent number
US06403575B1

Reaction notes

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