Boron trifluoride etherate → 6-(2-Chloro-5-((2S,3R,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-yl)benzyl)-2,3-dihydrobenzo[b][1,4]dioxine

HRID 576368Notes

Reaction equation

HRID 576368 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[S:11][C:10]1([C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[C:43]([CH2:48][C:49]2[CH:58]=[CH:57][C:52]3[O:53][CH2:54][CH2:55][O:56][C:51]=3[CH:50]=2)[CH:42]=1)O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.B(F)(F)F.CCOCC>ClCCl.C(#N)C>[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([C@H:10]2[C@H:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C@@H:14]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C@H:13]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[S:11]2)=[CH:42][C:43]=1[CH2:48][C:49]1[CH:58]=[CH:57][C:52]2[O:53][CH2:54][CH2:55][O:56][C:51]=2[CH:50]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 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-ol

Product 1

HCID 710785906-(2-Chloro-5-((2S,3R,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-yl)benzyl)-2,3-dihydrobenzo[b][1,4]dioxineYield 54%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred −15° C. solution of lactol (125, 410 mg, 0.50 mmol) in dichloromethane/acetonitrile (4 mL/4 mL) was added triethylsilane (0.49 mL, 3.02 mmol) followed by boron trifluoride diethyl etherate (0.26 mL, 2.01 mmol) at a rate such that the reaction temperature was maintained between −15 and 0° C. The solution was allowed to warm to 0° C. over 0.5 h prior to quenching with saturated sodium bicarbonate solution. After removal of organic volatiles under a reduced pressure, the residue was partitioned between ethyl acetate and water. Following extraction of the aqueous layer 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 25% ethyl acetate in hexane) to yield the title compound (126, 215 mg, 0.27 mmol, 53%) as a white solid.

Workup

  1. temperaturewas maintained between −15 and 0° C
  2. customto quenching with saturated sodium bicarbonate solution
  3. customAfter removal of organic volatiles under a reduced pressure
  4. customthe residue was partitioned between ethyl acetate and water
  5. extractionextraction of the aqueous layer 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 25% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-258a8e9eee1949599343f3dce7ad8d78
Source dataset
uspto-grants-2015_05
Patent number
US09034921B2

Reaction notes

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