Benzyl Alcohol → HCID 67121463, compound

HRID 406152Notes

Reaction equation

HRID 406152 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]([OH:49])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][CH: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].O.ON1C2C=CC=CC=2N=N1.[CH2:61](O)[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>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][CH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][CH: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

5

Reactant 3

HCID 244Benzyl AlcoholHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 67121463HCID 67121463, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (6R,6aS,14aR)-1,6,8,14a-tetrahydroxy-11-((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-carboxylic acid (80 mg, 0.12 mmol) in THF (1 mL) was added polystyrene-carbodiimide (208 mg, 0.24 mmol), 1-hydroxybenzotriazole hydrate (32 mg, 0.24 mmol) and benzyl alcohol (0.5 mL). The reaction mixture was stirred at room temperature under nitrogen for 17 h. The reaction was filtered through a micro filter and concentrated. The crude material was purified by preparative HPLC (10:90 acetonitrile/water to 60:40 acetonitrile/water with 0.05% TFA over 10 min, then isocratic) to afford (6R,6aS,14aR)-benzyl 1,6,8,14a-tetrahydroxy-11-((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 as a mixture of diastereomers (14 mg, 20%) and as a dark red solid: 1H NMR (500 MHz, CDCl3) δ 14.26 (s, 0.3H), 14.17 (s, 0.7H), 12.09 (s, 0.3H), 12.08 (s, 0.7H), 8.32 (br s, 6H), 8.27 (s, 0.3H), 8.21 (s, 0.7H), 6.86 (d, J=8.0 Hz, 1H), 6.52 (s, 1H), 5.87 (s, 0.7H), 5.86 (s, 0.3H), 5.28 (s, 2H), 4.96 (d, J=8.0 Hz, 1H), 4.67 (d, J=8.0 Hz, 1H), 3.80 (s, 3H), 3.74-3.70 (m, 2H), 3.61 (s, 3H), 3.58-3.53 (m, 2H), 3.40 (s, 3H), 3.37-3.30 (m, 3H), 3.13 (t, J=9.0 Hz, 1H), 2.41 (s, 2H), 3.39 (s, 1H), 1.36 (d, J=6.5 Hz, 3H); MS (ESI+) m/z 774 (M+H); HPLC >99% (AUC), tR 15.52 min.

Workup

  1. filtrationThe reaction was filtered through
  2. filtrationa micro filter
  3. concentrationconcentrated
  4. customThe crude material was purified by preparative HPLC (10:90 acetonitrile/water to 60:40 acetonitrile/water with 0.05% TFA over 10 min

Sources & evidence

ORD record
ord-6a0ee647cd6d4a6ca35449021fff7c58
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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