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

HRID 1159329Notes

Reaction equation

HRID 1159329 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-f241149cc18f463a863c83ba8bb5e739
Source dataset
uspto-grants-2010_10
Patent number
US07812028B2

Reaction notes

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