Hydrochloric Acid → 3-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyloxy)-4-{[4-(4-carboxybut-1-ynyl)phenyl]methyl}-5-isopropyl-1H-pyrazole

HRID 2223639Notes

Reaction equation

HRID 2223639 reaction equation
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=2)=[C:28]([CH:38]([CH3:40])[CH3:39])[NH:27][N:26]=1)(=[O:3])[CH3:2].[C:41]([OH:47])(=[O:46])[CH2:42][CH2:43][C:44]#[CH:45].Cl>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([C:45]#[C:44][CH2:43][CH2:42][C:41]([OH:47])=[O:46])=[CH:33][CH:32]=2)=[C:28]([CH:38]([CH3:40])[CH3:39])[NH:27][N:26]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 224644-Pentynoic acidHCID 685376403-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyloxy)-4-[(4-iodophenyl)methyl]-5-isopropyl-1H-pyrazole

Product 1

HCID 685411753-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyloxy)-4-{[4-(4-carboxybut-1-ynyl)phenyl]methyl}-5-isopropyl-1H-pyrazoleYield 90%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-[(4-iodophenyl)methyl]-5-isopropyl-1H-pyrazole (0.43 g), 4-pentynoic acid (94 mg), tetrakis(triphenylphosphine)palladium(0) (37 mg), copper(I)iodide (12 mg) and tiethylamine (0.45 mL) in tetrahydrofuran (5 mL) was stirred at room temperature under an argon atmosphere overnight. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/2-ethyl acetate) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-{[4-(4-carboxybut-1-ynyl)phenyl]methyl}-5-isopropyl-1H-pyrazole (0.37 g). This material was dissolved in N,N-dimethylformamide (6 mL). To the solution were added benzyl 2-amino-2-methylpropionate hydrochloride (0.15 g), 1-hydroxybenzotriazole (86 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.22 g) and triethylamine (0.32 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water, a saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-[(4-{4-[1-benzyloxycarbonyl-1-(methyl)-ethylcarbamoyl]but-1-ynyl}phenyl)methyl]-5-isopropyl-1H-pyrazole (0.36 g). This material was dissolved in methanol (5 mL). To the solution was added 10% palladium-carbon powder (50 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give the title compound (0.31 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/2-ethyl acetate)

Sources & evidence

ORD record
ord-9e4a0846d224451db9e17c69e6fbc7e0
Source dataset
uspto-grants-2008_05
Patent number
US07375087B2

Reaction notes

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