3-Buten-1-ol → 4-{4-[(1E)-4-hydroxybut-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside

HRID 1625936Notes

Reaction equation

HRID 1625936 reaction equation
[CH2:1]([OH:5])[CH2:2][CH:3]=[CH2:4].[C:6]([O:9][C@@H:10]1[C@@H:33]([O:34][C:35](=[O:37])[CH3:36])[C@H:32]([O:38][C:39](=[O:41])[CH3:40])[C@@H:31]([CH2:42][O:43][C:44](=[O:46])[CH3:45])[O:30][C@H:11]1[O:12][C:13]1[C:17]([CH2:18][C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][C:20]=2[CH3:26])=[C:16]([CH:27]([CH3:29])[CH3:28])[NH:15][N:14]=1)(=[O:8])[CH3:7].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:6]([O:9][C@@H:10]1[C@@H:33]([O:34][C:35](=[O:37])[CH3:36])[C@H:32]([O:38][C:39](=[O:41])[CH3:40])[C@@H:31]([CH2:42][O:43][C:44](=[O:46])[CH3:45])[O:30][C@H:11]1[O:12][C:13]1[C:17]([CH2:18][C:19]2[CH:24]=[CH:23][C:22](/[CH:4]=[CH:3]/[CH2:2][CH2:1][OH:5])=[CH:21][C:20]=2[CH3:26])=[C:16]([CH:27]([CH3:29])[CH3:28])[NH:15][N:14]=1)(=[O:8])[CH3:7]

Participants

7

Reactant 3

HCID 693893-Buten-1-olHCID 80271Tri-o-tolylphosphineHCID 685376803-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-bromo-2-methyl-phenyl)methyl]-5-isopropyl-1H-pyrazole

Product 1

HCID 867151534-{4-[(1E)-4-hydroxybut-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosideYield 50.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

Add 3-buten-1-ol (6.1 mL, 70 mmol) to a solution of 4-(4-bromo-2-methylbenzyl)-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside (15 g, 23.5 mmol) in acetonitrile (200 mL) and triethylamine (50 mL). Degas the solution with nitrogen over 10 minutes. Add tri-o-tolylphosphine (1.43 g, 4.7 mmol) and palladium acetate (526 mg, 2.35 mmol). After refluxing at 90° C. for 2 hours, cool and concentrate to remove the solvent under reduced pressure. Purify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/hexanes from 20-80% over 20 min, 330 g column) to provide the title compound (7.5 g, 11.9 mmol). MS (m/z): 631.2 (M+1), 629.2 (M−1).

Workup

  1. customDegas the solution with nitrogen over 10 minutes
  2. temperaturecool
  3. concentrationconcentrate
  4. customto remove the solvent under reduced pressure
  5. customPurify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/hexanes from 20-80% over 20 min, 330 g column)

Sources & evidence

ORD record
ord-a20fa3672e6146649b79c7b3eed5238c
Source dataset
uspto-grants-2014_07
Patent number
US08785404B2

Reaction notes

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