Benzoyl Peroxide → (6R,6aS,14aR)-methyl 4-bromo-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

HRID 406153Notes

Reaction equation

HRID 406153 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:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].[Br:51]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)Cl>[Br:51][C:5]1[C:6]2[CH2:23][C@@H:22]([OH:24])[C@:21]3([O:25][CH3:26])[C@:8]([OH:45])([C:7]=2[C:2]([OH:1])=[C:3]([C:47]([O:49][CH3:50])=[O:48])[C:4]=1[CH3:46])[C:9](=[O:44])[C:10]1[C:19](=[C:18]([OH:28])[C:17]2[C:16](=[O:29])[CH:15]=[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)[C:13](=[O:43])[C:12]=2[CH:11]=1)[C:20]3=[O:27]

Participants

5

Reactant 3

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 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 56600400(6R,6aS,14aR)-methyl 4-bromo-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-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
75 °C

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 (50 mg, 0.072 mmol) in chloroform (1 mL) was added N-bromosuccinimide (13 mg, 0.072 mmol) followed by benzoyl peroxide (1-2 mg). The reaction mixture was refluxed at 75° C. for 1 h. After cooled to room temperature, the reaction mixture was diluted with chloroform (10 mL) and washed with saturated sodium bicarbonate (5 mL). The aqueous layer was further extracted with chloroform (2×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by preparative TLC (silica gel, 95:5 chloroform/methanol) and semi-preparative HPLC to afford (6R,6aS,14aR)-methyl 4-bromo-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 (20 mg, 36%) as a dark red solid: 1H NMR (500 MHz, CDCl3) δ 14.22 (s, 1H), 11.62 (br s, 1H), 8.19 (s, 1H), 6.85 (d, J=9.0 Hz, 1H), 5.88 (s, 1H), 5.29 (s, 1H), 4.99 (s, 1H), 4.72 (s, 1H), 4.68 (d, J=8.5 Hz, 1H), 3.88 (s, 3H), 3.79 (s, 3H), 3.76-3.65 (m, 2H), 3.61 (s, 3H), 3.55 (d, J=6.5 Hz, 1H), 3.45 (d, J=20.5 Hz, 1H), 3.41 (s, 3H), 3.38-3.31 (m, 1H), 3.13 (t, J=9.5 Hz, 1H), 2.59 (s, 3H), 2.48 (d, J=4.5 Hz, 1H), 1.36 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 776 (M+H); HPLC >99% (AUC), tR 14.64 min.

Workup

  1. temperatureAfter cooled to room temperature
  2. washwashed with saturated sodium bicarbonate (5 mL)
  3. extractionThe aqueous layer was further extracted with chloroform (2×10 mL)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative TLC (silica gel, 95:5 chloroform/methanol) and semi-preparative HPLC

Sources & evidence

ORD record
ord-ac335c37afd343b5b7471c8d7e32e824
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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