Isoamyl Nitrite → 5-Bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

HRID 1929933Notes

Reaction equation

HRID 1929933 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8](N)=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[N:6]=1)=[O:4].N(OCCC(C)C)=O.C[Si](C)(C)[Br:29].C(=O)(O)[O-].[Na+]>BrCBr>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([Br:29])=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 8053Isoamyl NitriteHCID 76113BromotrimethylsilaneHCID 516892Sodium BicarbonateHCID 675046415-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

Product 1

HCID 866169575-Bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 3024DibromomethaneSolvent2×

Procedure

To a suspension of 5-amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester (1.26 g, 5.10 mmol, 1.0 eq) in dibromomethane (25 ml) was added isoamyl nitrite (0.85 ml, 6.29 mmol, 1.2 eq) at room temperature. The resulting suspension was added over 30 minutes at room temperature to a dibromomethane (5 ml) solution of trimethylbromosilane (0.82 ml, 5.90 mmol, 1.15 eq). The mixture was stirred for 2 hours at room temperature after which time the turbid solution was added to aqueous sodium bicarbonate (10%, 15 ml). The phases were mixed, separated and the organic layer dried over magnesium sulfate, concentrated in vacuo and purified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane to afford 5-Bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester as white crystals. Yield=0.81 g (51%). 1H NMR (250 MHz, DMSO): δ 3.92 (3H, s), 7.38 (2H, t, J=8.98 Hz), 7.76-7.81 (2H, m), 8.98 (1H, s). HPLC-MS=100%; 2.13 min (MW=311; M+1=313.0).

Workup

  1. additionThe phases were mixed
  2. customseparated
  3. dry with materialthe organic layer dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane

Sources & evidence

ORD record
ord-1a4ebfc6243a47288927a2a96e31a2ca
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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