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

HRID 611580Notes

Reaction equation

HRID 611580 reaction equation
B(F)(F)F.[CH3:5][CH2:6][O:7][CH2:8][CH3:9].NC1[CH:12]=[CH:13][C:14]([Br:17])=[N:15]C=1.N(OC(C)(C)C)=[O:19].C(Cl)Cl>COCCOC.CCCCC>[C:6]([O:7][C:8]1[CH:12]=[CH:13][C:14]([Br:17])=[N: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 5-amino-2-bromopyridine (from step 28a above) dissolved in 35 mL of DME. Then tert-butyl nitrite (14.7 mL, 125 mmol, Aldrich) was added at a rate which kept the temperature below 0° C. DME (65 mL) and CH2Cl2 (60 mL) were then added. After 10 minutes at -10° C. the mixture was warmed to 5° C. and stirred for 30 min. 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 acetic anhydride. The resulting solution was heated to 100° C.±5° C. for 1 hour. The solvent was removed in vacuro, 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:EtOAc to give 13.6 g of the title compound: 1H NMR (CDCl3 300 MHz) δ 2.35 (s, 3H) 7.36-7.39 (dd, 1H), 7.49-7.52 (d, 1H), 8.19-8.21 (d, 1H) MS m/z: 216 (M+H)+, 233 (M+NH4)+.

Workup

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

Sources & evidence

ORD record
ord-d18dcc0b3ec2431286706116c2500a17
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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