Benzoyl Peroxide → HCID 56600402, compound

HRID 406154Notes

Reaction equation

HRID 406154 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].[Cl:51]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:51][C:15]1[C:16](=[O:29])[C:17]2[C:18]([OH:28])=[C:19]3[C:10](=[CH:11][C:12]=2[C:13](=[O:43])[C:14]=1[NH:30][C@@H:31]1[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]1)[C:9](=[O:44])[C@:8]1([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]([C:47]([O:49][CH3:50])=[O:48])=[C:2]([OH:1])[C:7]=21)[C:20]3=[O:27]

Participants

5

Reactant 3

HCID 7187Benzoyl PeroxideHCID 31398Chlorosuccinimide2×HCID 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 56600402HCID 56600402, compoundYield 14%

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 (100 mg, 0.14 mmol) in chloroform (2 mL) was added N-chlorosuccinimide (28 mg, 0.21 mmol) followed by benzoyl peroxide (1-2 mg). The reaction mixture was refluxed at 75° C. for 12 h, and then N-chlorosuccinimide (19 mg, 0.14 mmol) was refilled and the reaction mixture was refluxed for another 5 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 10-chloro-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 (13.3 mg, 14%) as a red solid: 1H NMR (500 MHz, CDCl3) δ 13.72 (s, 1H), 12.11 (s, 1H), 8.22 (s, 1H), 7.11 (br s, 1H), 6.54 (s, 1H), 5.73 (s, 1H), 5.20 (s, 1H), 4.95 (s, 1H), 4.60 (s, 1H), 3.85 (s, 3H), 3.82 (s, 3H), 3.73 (s, 2H), 3.60 (s, 3H), 3.59-3.52 (m, 1H), 3.41 (s, 3H), 3.38-3.31 (m, 1H), 3.34 (d, J=19.5 Hz, 1H), 3.11 (t, J=9.5 Hz, 1H), 2.48 (br s, 1H), 2.41 (s, 3H), 1.36 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 732 (M+H); HPLC 95.1% (AUC), tR 14.34 min; and (6R,6aS,14aR)-methyl 4,10-dichloro-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 (3.6 mg, 3%) as a dark blue solid: 1H NMR (500 MHz, CDCl3) δ 13.72 (s, 1H), 11.70 (br s, 1H), 8.20 (s, 1H), 7.11 (br s, 1H), 5.71 (s, 1H), 5.26 (s, 1H), 5.00 (s, 1H), 4.71 (s, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.73 (s, 2H), 3.60 (s, 3H), 3.59-3.52 (m, 1H), 3.50-3.41 (m, 2H), 3.41 (s, 3H), 3.11 (t, J=9.0 Hz, 1H), 2.54 (s, 3H), 2.46 (s, 1H), 1.34 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 766 (M+H); HPLC 92.8% (AUC), tR 15.63 min.

Workup

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

Sources & evidence

ORD record
ord-a9768705cec246fab5b6f133069b1c4f
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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