Hydrogen Bromide → Methyl 3-bromonaphthalene-1-carboxylate

HRID 1010620Notes

Reaction equation

HRID 1010620 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[C:8]([C:16]([O:18][CH3:19])=[O:17])[C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2.[BrH:20]>O.C(O)C>[Br:20][C:6]1[CH:7]=[C:8]([C:16]([O:18][CH3:19])=[O:17])[C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2

Participants

6

Reactant 3

HCID 260Hydrogen Bromide2×HCID 23423661Methyl 3-aminonaphthalene-1-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 11311609Methyl 3-bromonaphthalene-1-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4.34 g (62.9 mmol) of sodium nitrite in 40 mL of water was added dropwise to a 0° C. solution of 11.5 g (57.2 mmol) of methyl 3-amino-1-naphthoate in 300 mL of ethanol and 60 mL of 48% aqueous hydrobromic acid while maintaining an internal reaction temperature below 10° C. After complete addition of the aqueous solution the resulting dark red reaction mixture was stirred at 0° C. for an additional 30 min. The cooled (0° C.) reaction mixture was then added over 20 min. to a suspension of 8.21 g (57.2 mmol) of cuprous bromide in 60 mL of ethanol and 60 mL of 48% aqueous hydrobromic acid heated to 95° C. After stirring for 30 min. the reaction mixture was cooled to 0° C. and carefully partitioned between ethyl ether (250 mL) and water (600 mL). The organic layer was separated and the aqueous layer was extracted with ethyl ether (2×300 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was passed through a plug of silica gel eluting with 30% dichloromethane in hexanes and the filtrate concentrated in vacuo. Flash chromatography on a Biotage® purification apparatus (silica gel, 7% dichloromethane/hexanes) yielded the title compound as a colorless solid. 1H NMR (DMSO-d6): δ 8.67 (d, J=8.4 Hz, 1 H), 8.50 (s, 1 H), 8.15 (s, 1 H), 8.02 (d, J=8.0 Hz, 1 H), 7.68-7.71 (m, 1 H), 7.63-7.66 (t, J=7.6 Hz, 1 H), 3.94 (s, 3H). LC/MS 265.0 (M+1) and 267.0 (M+3).

Workup

  1. temperaturewhile maintaining an internal reaction temperature below 10° C
  2. additionAfter complete addition of the aqueous solution
  3. customthe resulting dark red reaction mixture
  4. temperatureThe cooled
  5. custom(0° C.) reaction mixture
  6. temperatureheated to 95° C
  7. stirringAfter stirring for 30 min. the reaction mixture
  8. temperaturewas cooled to 0° C.
  9. customcarefully partitioned between ethyl ether (250 mL) and water (600 mL)
  10. customThe organic layer was separated
  11. extractionthe aqueous layer was extracted with ethyl ether (2×300 mL)
  12. washThe combined organic layers were washed with brine (100 mL)
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. concentrationthe filtrate concentrated in vacuo
  17. customFlash chromatography on a Biotage® purification apparatus (silica gel, 7% dichloromethane/hexanes)

Sources & evidence

ORD record
ord-36fea8f728ac46fc9b9ace49e3473ef0
Source dataset
uspto-grants-2011_07
Patent number
US07977339B2

Reaction notes

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