HCID 14803020, compound → (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-(4-chloro-3-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)phenyl)tetrahydro-2H-thiopyran-2-ol

HRID 2206740Notes

Reaction equation

HRID 2206740 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([CH:18]=1)[CH2:7][C:8]1[CH:17]=[CH:16][C:11]2[O:12][CH2:13][CH2:14][O:15][C:10]=2[CH:9]=1.C([Li])CCC.[CH2:25]([O:32][C@@H:33]1[C@@H:38]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@H:37]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@@H:36]([CH2:55][O:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[S:35][C:34]1=[O:64])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[CH2:25]([O:32][C@@H:33]1[C@@H:38]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@H:37]([O:47][CH2:48][C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[C@@H:36]([CH2:55][O:56][CH2:57][C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)[S:35][C:34]1([C:2]1[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([CH2:7][C:8]2[CH:17]=[CH:16][C:11]3[O:12][CH2:13][CH2:14][O:15][C:10]=3[CH:9]=2)[CH:18]=1)[OH:64])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 14803020HCID 14803020, compoundHCID 710784026-(5-Bromo-2-chlorobenzyl)-2,3-dihydrobenzo[b][1,4]dioxineHCID 178418339Butyllithium

Product 1

HCID 71078190(3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-(4-chloro-3-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)phenyl)tetrahydro-2H-thiopyran-2-olYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-(5-bromo-2-chlorobenzyl)-2,3-dihydrobenzo[b][1,4]dioxine (124, 384 mg, 1.1 mmol) in tetrahydrofuran (5 mL) at −78° C. under an atmosphere of nitrogen was added dropwise n-butyllithium (2.5 M in hexane, 0.45 mL, 1.1 mmol), and the mixture was stirred for 0.5 h at the same temperature. Then a solution of (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one (123, 300 mg, 0.54 mmol, This compound was synthesized by reference to H. Driguez and B. Henrissat, Tetrahedron Lett. 1981, 22, 5061-5062, Kakinuma, H., et al., J. Med. Chem. 2010, 53, 3247-3261) in tetrahydrofuran (5 mL) was added dropwise, and the mixture was stirred for 15 min at the same temperature. The reaction mixture was quenched by addition of saturated ammonium chloride solution. After complete addition, the solution was gradually raised to room temperature. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (silica gel, 3 to 30% tetrahydrofuran in hexane) to yield (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-(4-chloro-3-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)phenyl)tetrahydro-2H-thiopyran-2-ol (125, 416 mg, 0.51 mmol, 95%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 15 min at the same temperature
  2. customThe reaction mixture was quenched by addition of saturated ammonium chloride solution
  3. additionAfter complete addition
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by silica gel chromatography (silica gel, 3 to 30% tetrahydrofuran in hexane)

Sources & evidence

ORD record
ord-355ba0c37ab44b468e6828c9c334fa92
Source dataset
uspto-grants-2016_06
Patent number
US09371303B2

Reaction notes

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