p-Toluenesulfonic acid → HCID 59184885, compound

HRID 1943318Notes

Reaction equation

HRID 1943318 reaction equation
[OH:1][C:2]1[C:19]2[CH2:18][C@@:17]([OH:24])([C:20](=[O:23])[CH2:21][OH:22])[CH2:16][C@H:15]([O:25][C@@H:26]3[O:40][C@@H:39]([CH3:41])[C@H:29]4[O:30][C@H:31]5[N:36]([C@H:28]4[CH2:27]3)[CH2:35][CH2:34][O:33][C@@H:32]5[O:37][CH3:38])[C:14]=2[C:13]([OH:42])=[C:12]2[C:3]=1[C:4](=[O:46])[C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([O:44][CH3:45])[C:10]=1[C:11]2=[O:43].[O:47]1[CH:52]=[CH:51][CH2:50][CH2:49][CH:48]1[CH2:53][O:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>ClCCl.CO>[O:23]=[C:20]([C@@:17]1([OH:24])[CH2:16][C@H:15]([O:25][C@@H:26]2[O:40][C@@H:39]([CH3:41])[C@H:29]3[O:30][C@H:31]4[N:36]([C@H:28]3[CH2:27]2)[CH2:35][CH2:34][O:33][C@@H:32]4[O:37][CH3:38])[C:14]2[C:19](=[C:2]([OH:1])[C:3]3[C:4](=[O:46])[C:5]4[C:10]([C:11](=[O:43])[C:12]=3[C:13]=2[OH:42])=[C:9]([O:44][CH3:45])[CH:8]=[CH:7][CH:6]=4)[CH2:18]1)[CH2:21][O:22][CH:52]1[O:47][CH:48]([CH2:53][O:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:49][CH2:50][CH2:51]1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 9874188PNU-159682HCID 19070279HCID 19070279, compound

Product 1

HCID 59184885HCID 59184885, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (8S,10S)-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-10-{[(1S,3R,4aS,9S,9aR,10aS)-9-methoxy-1-methyloctahydro-1H-pyrano[4′,3′:4,5] [1,3] oxazolo[2,3-c][1,4]oxazin-3-yl]oxy}-7,8,9,10-tetrahydrotetracene-5,12-dione (50 mg, 0.078 mmol) [PNU-159682, formula IIA, prepared as reported in WO 9802446] in 4 ml of dry dichloromethane under argon atmosphere, ethyl (3,4-dihydro-2H-pyran-2-ylmethoxy)acetate from step 1 (118.5 mg, 0.592 mmol) and anhydrous p-toluenesulfonic acid (22.3 mg, 0.12 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours, until no starting material was detectable (TLC analysis, MeOH:CH2Cl2=0.3:9.7). Sodium bicarbonate 10% aqueous solution was then added to the reaction mixture and the aqueous phase was extracted with dichloromethane (4×20 ml).The combined organic phases were dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The residue was purified by flash column chromatography (MeOH:CH2Cl2=0.3:9.7) on silica gel (230-400 mesh), affording 41 mg (red wax, yield 62%) of 48, as a mixture of four diastereoisomers. MS (ESI): 842 [M+H]+. Retention time=7.47, 7.83 min (method 2).

Workup

  1. extractionthe aqueous phase was extracted with dichloromethane (4×20 ml).The combined organic phases
  2. dry with materialwere dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated under vacuum
  5. customThe residue was purified by flash column chromatography (MeOH:CH2Cl2=0.3:9.7) on silica gel (230-400 mesh)

Sources & evidence

ORD record
ord-e5935784541d464381a1496ca6635353
Source dataset
uspto-grants-2013_03
Patent number
US08389697B2

Reaction notes

Loading…