Sodium Carbonate → HCID 101656270, compound

HRID 553429Notes

Reaction equation

HRID 553429 reaction equation
ClC1C=C(C=CC=1)C(OO)=[O:6].[CH3:12][CH2:13][C:14]1[CH2:31][N:29]2[CH2:30][C@H:16]([CH2:17][C@:18]([C:65]([O:67][CH3:68])=[O:66])([C:32]3[CH:33]=[C:34]4[C@:42]56[C@@H:46]7[C@:47]([CH2:62][CH3:63])([C@@H:51]([O:58][C:59]([CH3:61])=[O:60])[C@:52]([OH:57])([C:53]([O:55][CH3:56])=[O:54])[C@@H:41]5[N:40]([CH3:64])[C:35]4=[CH:36][C:37]=3[O:38][CH3:39])[CH:48]=[CH:49][CH2:50][N:45]7[CH2:44][CH2:43]6)[C:19]3[NH:27][C:26]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:20]=3[CH2:28]2)[CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[CH3:12][CH2:13][C:14]1[CH2:31][N:29]2[CH2:30][C@@H:16]([CH2:17][C@:18]([C:65]([O:67][CH3:68])=[O:66])([C:32]3[CH:33]=[C:34]4[C@@:42]56[C@@H:41]([N:40]([CH3:64])[C:35]4=[CH:36][C:37]=3[O:38][CH3:39])[C@@:52]([OH:57])([C:53]([O:55][CH3:56])=[O:54])[C@H:51]([O:58][C:59]([CH3:61])=[O:60])[C@:47]3([CH2:62][CH3:63])[CH:48]=[CH:49][CH2:50][N:45]([C@H:46]53)[CH2:44][CH2:43]6)[C:19]3[NH+:27]([O-:6])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]=3[CH2:28]2)[CH:15]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 70297m-Chloroperbenzoic acidHCID 5311497Vinorelbine

Product 1

HCID 101656270HCID 101656270, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

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.

Workup

  1. extractionwas extracted by CHCl3 (20 mL)
  2. dry with materialAfter drying over sodium sulfate and filtration
  3. extractionthe CHCl3 extract
  4. customwas evaporated under reduced pressure

Sources & evidence

ORD record
ord-a0fa00421ff243d5b1fdfbeb3c503b18
Source dataset
uspto-grants-2011_11
Patent number
US08048872B2

Reaction notes

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