Trimethylsilyl triflate → [(5S)-3-(5-bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside

HRID 459058Notes

Reaction equation

HRID 459058 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:12][C@@H:11]([CH2:13][OH:14])[O:10][N:9]=2)=[N:6][CH:7]=1.[C:15]([O:18][C@@H:19]1[C@@H:31]([O:32][C:33](=[O:35])[CH3:34])[C@H:30]([O:36][C:37](=[O:39])[CH3:38])[C@@H:29]([CH2:40][O:41][C:42](=[O:44])[CH3:43])[O:28][C@@H:20]1OC(=N)C(Cl)(Cl)Cl)(=[O:17])[CH3:16].FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClCCl>[C:15]([O:18][C@@H:19]1[C@@H:31]([O:32][C:33](=[O:35])[CH3:34])[C@H:30]([O:36][C:37](=[O:39])[CH3:38])[C@@H:29]([CH2:40][O:41][C:42](=[O:44])[CH3:43])[O:28][C@H:20]1[O:14][CH2:13][C@H:11]1[O:10][N:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)[CH2:12]1)(=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 10896298alpha-D-Glucopyranose, 2,3,4,6-tetraacetate 1-(2,2,2-trichloroethanimidate)HCID 586537515-Bromo-2-[(5S)-5-hydroxymethyl-4,5-dihydroisoxazol-3-yl]pyridine2×

Product 1

HCID 69153413[(5S)-3-(5-bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [(5S)-3-(5-bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methanol (Intermediate 11, 0.369 g, 1.43 mmol) and 2,3,4,6-tetra-O-acetyl-1-O-(2,2,2-trichloroethanimidoyl)-α-D-glucopyranose (R. R. Schmidt and J. Michel, Angew. Chem. Int. Ed. Engl. 19 (1980), 731–732) in dry dichloromethane (20 mL) over molecular sieves (perled, 4 Å) was added dropwise at −20° C. a solution of trimethylsilyl trifluoromethanesulfonate in dichloromethane (0.02 M, 10 mL). The reaction mixture was allowed to reach room temperature over 2 hours, additional catalyst solution (5 mL) was added and it was left overnight at room temperature. The reaction was quenched by addition of triethylamine (3 drops), filtered and solvent was removed under reduced pressure. Chromatography on silica gel with hexanes/acetone 2:1 gave crude [(5S)-3-(5-bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside, as a mixture with intermediate 11. To a solution of this mixture in dry methanol (5 mL) was added potassium carbonate (20 mg) and it was vigorously stirred for 4 hours at room temperature. The reaction mixture was neutralized over Amberlite CG-50-II (H+-form), filtered and solvent was removed under reduced pressure. Chromatography on silica gel with dichloromethane/methanol 8:1 gave the product as a colourless solid (157 mg).

Workup

  1. waitit was left overnight at room temperature
  2. customThe reaction was quenched by addition of triethylamine (3 drops)
  3. filtrationfiltered
  4. customsolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-b4904d6393ed48789309c380397ac059
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Reaction notes

Loading…