Hydroxyamine hydrochloride → HCID 178497454, compound

HRID 406158Notes

Reaction equation

HRID 406158 reaction equation
[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([O:49][CH3:50])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][C@@H:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=O)[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].Cl.[NH2:52][OH:53]>CO.N1C=CC=CC=1.C(OCC)(=O)C>[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([O:49][CH3:50])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][C@@H:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15]/[C:16](=[N:52]\[OH:53])/[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44]

Participants

6

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 67121454(6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate

Product 1

HCID 178497454HCID 178497454, compoundYield 16.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (100 mg, 0.143 mmol) in methanol (1 mL) and pyridine (1 mL) was added hydroxylamine hydrochloride (100 mg, 1.43 mmol) at room temperature, and the mixture was stirred under nitrogen overnight. The mixture was diluted with ethyl acetate, washed with 1N HCl and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by preparative TLC (silica gel, 95:5 chloroform/methanol) to afford (6R,6aS,14aR,E)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-9-(hydroxyimino)-6a-methoxy-3-methyl-7,12,14-trioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (17 mg, 16%) as an orange solid: 1H NMR (500 MHz, CDCl3) δ 12.02 (s, 1H), 8.45 (s, 1H), 6.93 (s, 1H), 6.54 (s, 1H), 6.52 (d, J=9.0 Hz, 1H), 5.33 (br s, 1H), 5.00 (br s, 1H), 4.84-4.82 (m, 2H), 3.83 (s, 3H), 3.80 (s, 3H), 3.78-3.68 (m, 3H), 3.62 (s, 3H), 3.54 (dd, J=19.5, 6.5 Hz, 1H), 3.45-3.42 (m, 1H), 3.43 (s, 3H), 3.36 (d, J=19.5 Hz, 1H), 3.13 (t, J=9.5 Hz, 1H), 2.46 (d, J=5.0 Hz, 1H), 2.39 (s, 3H), 1.38 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 713 (M+H); HPLC 95.0% (AUC), tR 12.31 min.

Workup

  1. washwashed with 1N HCl and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by preparative TLC (silica gel, 95:5 chloroform/methanol)

Sources & evidence

ORD record
ord-e075d7d1d48c457c91e05f0f057baaf2
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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