Benzyl Bromide → (6R,6aS,14aR)-methyl 1-(benzyloxy)-6,8,14a-trihydroxy-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 406134Notes

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].C(=O)([O-])[O-].[K+].[K+].[CH2:57](Br)[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>>[CH2:57]([O: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])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1

Participants

Reactant 3

HCID 7498Benzyl Bromide

HCID 11430Potassium Carbonate

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 56601388(6R,6aS,14aR)-methyl 1-(benzyloxy)-6,8,14a-trihydroxy-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 45.7%

Procedure

Following General Procedure: Method A using (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 (35 mg, 0.050 mmol), potassium carbonate (21 mg, 0.15 mmol) and benzyl bromide (18 μL, 0.15 mmol), the product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol) to afford (6R,6aS,14aR)-methyl 1-(benzyloxy)-6,8,14a-trihydroxy-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 (18 mg, 45%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 14.17 (s, 1H), 7.82 (s, 1H), 7.46-7.44 (m, 2H), 7.40-7.38 (m, 1H), 7.34-7.32 (m, 2H), 6.85 (s, 1H), 6.81 (d, J=8.6 Hz, 1H), 5.86 (s, 1H), 5.07 (br s, 1H), 4.98-4.94 (m, 1H), 4.93 (d, J=11.3 Hz, 1H), 4.82 (d, J=11.3 Hz, 1H), 4.68 (d, J=8.8 Hz, 1H), 4.54 (d, J=10.5 Hz, 1H), 3.82 (s, 3H), 3.74-3.72 (m, 2H), 3.65-3.62 (m, 1H), 3.60 (s, 3H), 3.54 (s, 3H), 3.51-3.38 (m, 1H), 3.39 (s, 3H), 3.36-3.32 (m, 1H), 3.13 (t, J=9.0 Hz, 1H), 2.48 (d, J=4.1 Hz, 1H), 2.19 (s, 3H), 1.36 (d, J=6.2 Hz, 3H); MS (ESI+) m/z 788 (M+H); HPLC 95.4% (AUC), tR 14.56 min.

Workup

customthe product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol)

Sources & evidence

ORD record: ord-8d4b105004be4d93958c9865b5638600
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754054B2

Reaction notes

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