Diethyl Ether → HCID 56601390, compound

HRID 406166Notes

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].[CH3:51][Mg]Br.C(OCC)C>C1COCC1>[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]([OH:43])([CH3:51])[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]

Participants

Conditions

Temperature: -78 °C

Procedure

To a −78° C. 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 THF (4 mL) was added a solution of methylmagnesium bromide in diethyl ether (3 M, 0.37 mL, 1.12 mmol) dropwise. The reaction mixture was stirred at −78° C. for 5 h, and then quenched with a saturated solution of ammonium chloride. The mixture was extracted with chloroform (3×20 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude was purified by preparative TLC (silica gel, 95:5 chloroform/methanol), and then the diastereomers were separated by preparative HPLC (Chiralpak AD column, 40:60 heptane/ethanol with 0.1% diethylamine) to afford (6R,6aS,14aR)-methyl 1,6,8,12,14a-pentahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3,12-dimethyl-7,9,14-trioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (diastereomer A, 39 mg, 39%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 15.20 (br s, 1H), 11.75 (br s, 1H), 7.82 (s, 1H), 6.78 (s, 1H), 6.53 (s, 1H), 5.45 (s, 1H), 5.22 (s, 1H), 4.96 (s, 1H), 4.80-4.61 (m, 2H), 3.81 (s, 3H), 3.76 (s, 3H), 3.71 (dd, J=9.0, 2.5 Hz, 1H), 3.64 (s, 1H), 3.60 (s, 3H), 3.59-3.52 (m, 1H), 3.42 (s, 3H), 3.35-3.29 (m, 2H), 3.16 (t, J=9.0 Hz, 1H), 2.95 (br s, 1H), 2.48 (br s, 1H), 2.38 (s, 3H), 1.79 (s, 3H), 1.37 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 714 (M+H); HPLC >99% (AUC), tR 11.18 min; and (6R,6aS,14aR)-methyl 1,6,8,12,14a-pentahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3,12-dimethyl-7,9,14-trioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (diastereomer B, 13 mg, 13%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 15.10 (br s, 1H), 12.02 (br s, 1H), 7.84 (s, 1H), 6.73 (d, J=8.5 Hz, 1H), 6.54 (s, 1H), 5.48 (s, 1H), 5.25 (s, 1H), 4.98 (s, 1H), 4.78-4.63 (m, 2H), 3.85 (s, 3H), 3.79 (s, 3H), 3.72 (s, 2H), 3.59 (s, 5H), 3.38 (s, 4H), 3.32 (d, J=19.0 Hz, 1H), 3.10 (t, J=9.0 Hz, 1H), 2.49 (br s, 1H), 2.41 (s, 3H), 1.65 (s, 3H), 1.32 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 714 (M+H); HPLC 98.1% (AUC), tR 11.45 min.

Workup

customquenched with a saturated solution of ammonium chloride
extractionThe mixture was extracted with chloroform (3×20 mL)
dry with materialThe combined organics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude was purified by preparative TLC (silica gel, 95:5 chloroform/methanol)
customthe diastereomers were separated by preparative HPLC (Chiralpak AD column, 40:60 heptane/ethanol with 0.1% diethylamine)

Sources & evidence

ORD record: ord-524b7af077474772a4fae51d9220e625
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754054B2

Reaction notes

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