Reaction #640611

Reaction equation

m-Chloroperoxybenzoic acid

vinorelbine

sodium carbonate

→

vinorelbine N-oxide

Yield 83.0%

Solvents

CHCl3

CHCl3

Conditions

Workup

1. 1
   Extractionwas extracted by CHCl3 (20 mL)
2. 2
   DryingAfter drying over sodium sulfate and filtration
3. 3
   Extractionthe CHCl3 extract
4. 4
   Otherwas evaporated under reduced pressure

Procedure

Vinorelbine N′b-oxide was synthesized using essentially the same procedure used to prepare vinblastine N′b-oxide. m-Chloroperoxybenzoic acid (45 mg, 0.26 mmol) in CHCl3 (2.5 mL) was added at 0° to a stirred solution of purified vinorelbine (150 mg, 0.20 mmol) in CHCl3 (4.5 mL) under nitrogen. After 15 min, the mixture was poured into an aqueous sodium carbonate (27 mL, 40 g/L) and was extracted by CHCl3 (20 mL). After drying over sodium sulfate and filtration, the CHCl3 extract was evaporated under reduced pressure affording crude vinorelbine N-oxide (125 mg, 83%). Thin-layer chromatography (silica; 9:1 CHCl3/MeOH) indicated the presence of a small amount of starting vinorelbine (vinorelbine Rf=0.37, vinorelbine N′b-oxide Rf=0.18). Radial chromatography on silica gel (eluent, 9:1 CHCl3/MeOH) gave vinorelbine N′b-oxide as an off-white solid (100 mg; 75%). The sample was dissolved in ethyl acetate/hexanes and then the open flask was placed in a sealed container containing an open flask of hexanes. As the hexanes diffused slowly into the vinorelbine N′b-oxide solution, vinorelbine N′b-oxide precipitated out as an off-white powder (80 mg; 53%). The 300 MHz 1HNMR spectrum was consistent with the assigned structure. The configuration of the N′b-oxide oxygen atom is assigned the same stereochemistry as that found in vinblastine N-oxide by x-ray crystallography.

Source