Ammonium Chloride → 4-(difluoromethyl)phenyl 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl) indol-3-yl methanol

HRID 544886Notes

Reaction equation

HRID 544886 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH:9]([F:11])[F:10])=[CH:5][CH:4]=1.[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[C:15]([CH:45]=[O:46])=[CH:16][N:17]2[C@@H:22]1[O:39][C@H:38]([CH2:40][O:41][C:42](=[O:44])[CH3:43])[C@@H:33]([O:34][C:35](=[O:37])[CH3:36])[C@H:28]([O:29][C:30](=[O:32])[CH3:31])[C@H:23]1[O:24][C:25](=[O:27])[CH3:26].[Cl-].[NH4+]>O1CCCC1.BrCCBr>[F:10][CH:9]([F:11])[C:6]1[CH:7]=[CH:8][C:3]([CH:45]([C:15]2[C:14]3[C:18](=[CH:19][CH:20]=[CH:21][C:13]=3[F:12])[N:17]([C@@H:22]3[O:39][C@H:38]([CH2:40][O:41][C:42](=[O:44])[CH3:43])[C@@H:33]([O:34][C:35](=[O:37])[CH3:36])[C@H:28]([O:29][C:30](=[O:32])[CH3:31])[C@H:23]3[O:24][C:25](=[O:27])[CH3:26])[CH:16]=2)[OH:46])=[CH:4][CH:5]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27611831-Bromo-4-(difluoromethyl)benzeneHCID 5462224Magnesium2×HCID 715002594-fluoro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)indole-3-carboxaldehyde

Product 1

HCID 671961774-(difluoromethyl)phenyl 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl) indol-3-yl methanol

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of magnesium turnings (71 mg) in tetrahydrofuran (2 ml) was added dropwise a solution of 1-bromo-4-difluoromethylbenzene (587 mg) in tetrahydrofuran (1.5 ml) under being stirred vigorously. The mixture was warmed with a dryer, and thereto was added 1,2-dibromoethane (4 drops). The resultant mixture was vigorously stirred at room temperature till a disappearance of magnesium turnings, and then dropwise added to a solution of the above 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carboxaldehyde (350 mg) in tetrahydrofuran (4 ml) over 10 minutes at −78° C. under argon atmosphere. The mixture was stirred at same temperature for 1 hour, and thereto was added a saturated aqueous ammonium chloride solution (20 ml). The resultant mixture was extracted with ethyl acetate (50 ml) 3 times, and the combined organic layer was dried over magnesium sulfate. The insoluble materials were filtered off, and the filtrate was evaporated under reduced pressure to give crude 4-(difluoromethyl)phenyl 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl methanol, which was used in the subsequent step without further purification.

Workup

  1. temperatureThe mixture was warmed with a dryer
  2. stirringThe mixture was stirred at same temperature for 1 hour
  3. extractionThe resultant mixture was extracted with ethyl acetate (50 ml) 3 times
  4. dry with materialthe combined organic layer was dried over magnesium sulfate
  5. filtrationThe insoluble materials were filtered off
  6. customthe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-01143a2ee3894bd5b3b39dc2022b900e
Source dataset
uspto-grants-2011_05
Patent number
US07935674B2

Reaction notes

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