Potassium Carbonate → (6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-1-(2-methoxy-2-oxoethoxy)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate

HRID 406133Notes

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+].Br[CH2:58][C:59]([O:61][CH3:62])=[O:60]>>[OH:24][C@H:22]1[C@:21]2([O:25][CH3:26])[C@@:8]([OH:45])([C:9](=[O:44])[C:10]3[C:19]([C:20]2=[O:27])=[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]=3)[C:7]2[C:2]([O:1][CH2:58][C:59]([O:61][CH3:62])=[O:60])=[C:3]([C:47]([O:49][CH3:50])=[O:48])[C:4]([CH3:46])=[CH:5][C:6]=2[CH2:23]1

Participants

Reactant 3

HCID 11430Potassium Carbonate

HCID 60984Methyl bromoacetate

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 56601584(6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-1-(2-methoxy-2-oxoethoxy)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylateYield 20%

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 (50 mg, 0.072 mmol), potassium carbonate (30 mg, 0.22 mmol) and methyl bromoacetate (20 μL, 0.22 mmol), the product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol) and semi-preparative HPLC (45:55 acetonitrile/water with 0.05% TFA) to afford (6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-1-(2-methoxy-2-oxoethoxy)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (10 mg, 20%) as a red solid: 1H NMR (500 MHz, CDCl3) δ 14.19 (s, 1H), 8.27 (s, 1H), 6.89 (d, J=9.0 Hz, 1H), 6.86 (s, 1H), 5.88 (s, 1H), 4.96 (d, J=6.6 Hz, 1H), 4.69 (d, J=8.7 Hz, 1H), 4.54 (d, J=15.1 Hz, 1H), 4.43 (d, J=15.1 Hz, 1H), 3.91 (br s, 3H), 3.79 (s, 3H), 3.76-3.67 (m, 3H), 3.73 (s, 3H), 3.64-3.55 (m, 1H), 3.60 (s, 3H), 3.39 (s, 3H), 3.36-3.29 (m, 3H), 3.13 (t, J=9.2 Hz, 1H), 2.60 (br s, 1H), 2.19 (s, 3H), 1.36 (d, J=6.2 Hz, 3H); MS (ESI+) m/z 770 (M+H); HPLC 96.4% (AUC), tR 15.46 min.

Workup

customthe product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol) and semi-preparative HPLC (45:55 acetonitrile/water with 0.05% TFA)

Sources & evidence

ORD record: ord-cbf9dc92c1e64184a7c7fe6889d05934
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754054B2

Reaction notes

Loading…