Dichloromethane → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-bromo-2-methyl-phenyl)methyl]-5-isopropyl-1H-pyrazole

HRID 1625934Notes

Reaction equation

HRID 1625934 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([OH:17])=[N:11][NH:12][C:13]=2[CH:14]([CH3:16])[CH3:15])=[C:4]([CH3:18])[CH:3]=1.[C:19]([O:22][C@@H:23]1[C@@H:28]([O:29][C:30](=[O:32])[CH3:31])[C@H:27]([O:33][C:34](=[O:36])[CH3:35])[C@@H:26]([CH2:37][O:38][C:39](=[O:41])[CH3:40])[O:25][C@@H:24]1Br)(=[O:21])[CH3:20].ClCCl.C(=O)([O-])[O-].[K+].[K+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)C1C=CC=CC=1.O>[C:19]([O:22][C@@H:23]1[C@@H:28]([O:29][C:30](=[O:32])[CH3:31])[C@H:27]([O:33][C:34](=[O:36])[CH3:35])[C@@H:26]([CH2:37][O:38][C:39](=[O:41])[CH3:40])[O:25][C@H:24]1[O:17][C:10]1[C:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[CH3:18])=[C:13]([CH:14]([CH3:15])[CH3:16])[NH:12][N:11]=1)(=[O:21])[CH3:20]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 101776alpha-D-Glucopyranosyl bromide, tetraacetateHCID 178422431HCID 178422431, compound

Product 1

HCID 685376803-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-bromo-2-methyl-phenyl)methyl]-5-isopropyl-1H-pyrazoleYield 73.5%

Reagents, catalysts & solvents 2

HCID 159952Benzyltributylammonium chlorideCatalystHCID 962WaterSolvent

Procedure

To a 1 L flask, add 4-[(4-bromo-2-methyl-phenyl)methyl]-5-isopropyl-1H-pyrazol-3-ol (24 g, 77.6 mmol), 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (50.4 g, 116 mmol), benzyltributylammonium chloride (5 g, 15.5 mmol), dichloromethane (250 mL), potassium carbonate (32 g, 323 mmol), and water (120 mL). Stir the reaction mixture overnight at room temperature. Extract with dichloromethane (450 mL). Wash the extract with water (300 mL) and brine (500 mL). Dry the organic phase over sodium sulfate, filter, and concentrate under reduced pressure. Purify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 10-70% over 20 min, 330 g column) to provide the title compound (36.5 g, 57 mmol). MS (m/z): 638.5 (M+1), 636.5 (M−1).

Workup

  1. extractionExtract with dichloromethane (450 mL)
  2. washWash the
  3. extractionextract with water (300 mL) and brine (500 mL)
  4. dry with materialDry the organic phase over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 10-70% over 20 min, 330 g column)

Sources & evidence

ORD record
ord-fb1cf3471bec4ac98f3cbd59ccf0b1d5
Source dataset
uspto-grants-2014_07
Patent number
US08785404B2

Reaction notes

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