p-Toluenesulfonic acid → (3'r,4's,5's,6'r,7s)-1-Benzenesulfonyl-3',4',5'-tris-benzyloxy-6'-benzyloxymethyl-3',4',5',6'-tetrahydro-spiro[furo[3,4,f]indole-7(5h),2'-[2h]pyran]

HRID 221929Notes

Reaction equation

HRID 221929 reaction equation
[CH:1]([Mg]Br)([CH3:3])[CH3:2].[CH2:6]([Li])[CH2:7][CH2:8]C.CCCCCC.C1([S:23]([N:26]2[C:34]3[C:29](=[CH:30][C:31]([CH2:36]OC(OC)(C)C)=[C:32](Br)[CH:33]=3)[CH:28]=[CH:27]2)(=[O:25])=[O:24])C=CC=CC=1.[CH2:43]([O:50][CH:51]1[CH:56]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:55]([O:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[CH:54]([CH2:73][O:74][CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[O:53][C:52]1=[O:82])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[Cl-].[NH4+].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.CO>[C:1]1([S:23]([N:26]2[C:34]3[C:29](=[CH:30][C:31]4[CH2:36][O:82][C@@:52]5([C@H:51]([O:50][CH2:43][C:44]6[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=6)[C@@H:56]([O:57][CH2:58][C:59]6[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=6)[C@@H:55]([O:65][CH2:66][C:67]6[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=6)[C@@H:54]([CH2:73][O:74][CH2:75][C:76]6[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=6)[O:53]5)[C:32]=4[CH:33]=3)[CH:28]=[CH:27]2)(=[O:25])=[O:24])[CH:3]=[CH:8][CH:7]=[CH:6][CH:2]=1

Participants

10

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 45855083,4,5-Tribenzyloxy-6-(benzyloxymethyl)tetrahydropyran-2-oneHCID 594887731-benzenesulfonyl-6-bromo-5-(1-methoxy-1-methyl-ethoxymethyl)-1H-indoleHCID 178418339ButyllithiumHCID 178418365HCID 178418365, compound

Product 1

HCID 68508213(3'r,4's,5's,6'r,7s)-1-Benzenesulfonyl-3',4',5'-tris-benzyloxy-6'-benzyloxymethyl-3',4',5',6'-tetrahydro-spiro[furo[3,4,f]indole-7(5h),2'-[2h]pyran]Yield 27%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent5×

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen stream, to THF (1.4 mL) were added a solution of isopropyl magnesium bromide in THF (0.65 M, 0.78 mL, 0.51 mmol) and a solution of n-butyllithium in n-hexane (1.58 M, 645 μL, 1.02 mmol) under ice cooling, and the resultant solution was stirred for 30 minutes. The solution was then cooled to −78° C., and a solution of 1-benzenesulfonyl-6-bromo-5-(1-methoxy-1-methyl-ethoxymethyl)-1H-indole (186 mg, 0.42 mmol) in THF (0.75 mL) was added dropwise thereto. The resultant mixture was then stirred for 1 hour. A solution of 3,4,5-tris-benzyloxy-6-(benzyloxymethyl)-tetrahydro-pyran-2-one (686 mg, 1.27 mmol) in THF (0.75 mL) was added dropwise to the reaction mixture at the same temperature. The resultant mixture was stirred for 1 hour at −20° C., and then saturated aqueous ammonium chloride was added. The resultant mixture was extracted with dichloromethane, and the organic layer was dried (anhydrous magnesium sulfate). Solvent was then removed by distillation under reduced pressure. To the resulting residue was added THF (1.6 mL), methanol (1 mL) and p-toluenesulfonic acid (47 mg, 0.25 mmol), and the resultant mixture was stirred for 2 hours at room temperature. Solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by silica gel flash column chromatography (developing solution=ethyl acetate:n-hexane (1:1)), to thereby obtain the titled compound (92 mg, 27%).

Workup

  1. extractionThe resultant mixture was extracted with dichloromethane
  2. dry with materialthe organic layer was dried (anhydrous magnesium sulfate)
  3. customSolvent was then removed by distillation under reduced pressure
  4. customSolvent was then removed by distillation under reduced pressure
  5. customthe resulting residue was purified by silica gel flash column chromatography (developing solution=ethyl acetate:n-hexane (1:1))

Sources & evidence

ORD record
ord-7bf7ccc6d7b44307b110d83bce7f9cdf
Source dataset
uspto-grants-2012_06
Patent number
US08207134B2

Reaction notes

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