Chlorotrimethylsilane → Methyl 6-(cyclohexylamino)-5-nitronicotinate

HRID 392980Notes

Reaction equation

HRID 392980 reaction equation
[CH:1]1([NH:7][C:8]2[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[Si](C)(C)[CH3:22]>CO>[CH:1]1([NH:7][C:8]2[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:11]([C:12]([O:14][CH3:22])=[O:13])=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6397Chlorotrimethylsilane2×HCID 226607816-(Cyclohexylamino)-5-nitronicotinic acid

Product 1

HCID 22660792Methyl 6-(cyclohexylamino)-5-nitronicotinateYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of intermediate 57 (9.7 g, 32.2 mmol) in methanol (400 mL) was added chlorotrimethylsilane (3 mL) to achieve pH=2. The reaction mixture was heated at strong reflux for 72 h, during which time the pH was monitored and more chlorotrimethylsilane added as necessary to maintain an acidic solution. The reaction mixture was allowed to cool and was then concentrated on a rotary evaporator. The residue was purified by column chromatography (silica gel, 7:2:1 hexanes/dichloromethane/methanol) to afford the crude ester as a yellow solid (9.0 g, 89%). ESI-MS m/e 280.1 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat strong reflux for 72 h, during which time the pH
  3. temperatureto maintain an acidic solution
  4. temperatureto cool
  5. concentrationwas then concentrated on a rotary evaporator
  6. customThe residue was purified by column chromatography (silica gel, 7:2:1 hexanes/dichloromethane/methanol)

Sources & evidence

ORD record
ord-437bcbb96a0d44e6b31e4f90f94328c5
Source dataset
uspto-grants-2004_10
Patent number
US06803374B2

Reaction notes

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