Diisopropylamine → HCID 68745334, compound

HRID 2354279Notes

Reaction equation

HRID 2354279 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C@@H:21]1[C@@H:26]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@H:25]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@@H:24]([CH2:43][O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[O:23][C@H:22]1[C:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[N:54]([S:61]([C:64]2[CH:69]=[CH:68][C:67]([CH3:70])=[CH:66][CH:65]=2)(=[O:63])=[O:62])[CH:53]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:81])(=O)=O)=CC=1.[Cl-].[NH4+]>O1CCCC1>[CH2:13]([O:20][C@@H:21]1[C@@H:26]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C@H:25]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C@@H:24]([CH2:43][O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[O:23][C@H:22]1[C:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[N:54]([S:61]([C:64]2[CH:65]=[CH:66][C:67]([CH3:70])=[CH:68][CH:69]=2)(=[O:63])=[O:62])[C:53]=1[F:81])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 68744510HCID 68744510, compoundHCID 178418339Butyllithium

Product 1

HCID 68745334HCID 68745334, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-bromo-1-(toluene-4-sulfonyl)-1H-indole (1.22 g) in tetra hydrofuran (25 mL) was added n-butyl lithium (2.59 mol/L n-hexane solution, 1.24 mL) at −78° C., and the mixture was stirred at the same temperature for 30 minutes. To this mixture was added a solution of 2,3,4,6-tetra-O-benzyl-D-glucono-1,5-lactone (1.5 g) in tetra hydrofuran (7 mL) at the same temperature, and the mixture was stirred at the same temperature for 10 minutes, and stirred under ice-cooling for 1 hour. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with 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: n-hexane/ethyl acetate=5/1-3/1) to give the corresponding adduct (2.2 g). This material was dissolved in acetonitrile (27 mL). To the solution was added triethylsilane (0.87 mL). To the mixture was added boron trifluoride diethyl ether complex (0.38 mL) at −15° C., and the mixture was stirred at the same temperature for 15 minutes, and stirred at room temperature for 1 hour. To the reaction mixture was added 20% aqueous potassium carbonate solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with water 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: n-hexane/ethyl acetate=5/1) to give 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-(toluene-4-sulfonyl)-1H-indole (1.59 g). To a solution of diisopropylamine (0.026 mL) in tetra hydrofuran (3 mL) was added n-butyl lithium (2.67 mol/L n-hexane solution, 0.063 mL) at −78° C., and the mixture was stirred at the same temperature for 15 minutes. To this mixture was added a solution of 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-(toluene-4-sulfonyl)-1H-indole (0.11 g) in tetra hydrofuran (1 mL) at the same temperature, and the mixture was stirred at the same temperature for 30 minutes. To this mixture was added N-fluorobenzenesulfonimide (0.13 g) at the same temperature, and the mixture was stirred at the same temperature for 30 minutes, and stirred at room temperature for 1 hour. The reaction mixture was poured into a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with water 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: n-hexane/ethyl acetate=6/1) to give 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-fluoro-1-(toluene-4-sulfonyl)-1H-indole (57 mg). This material was dissolved in a mixed solvent of ethanol (2 mL) and tetra hydrofuran (1 mL). To the solution was added potassium hydroxide (79 mg), and the mixture was stirred at 50° C. overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid (3 mL), and the resulting mixture was extracted with ethyl acetate. The extract was washed with water 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: n-hexane/ethyl acetate=3/1) to give the title compound (35 mg).

Workup

  1. stirringthe mixture was stirred at the same temperature for 30 minutes
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. stirringstirred at room temperature for 1 hour
  4. extractionthe resulting mixture was extracted with diethyl ether
  5. washThe extract was washed with water and brine successively
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1)

Sources & evidence

ORD record
ord-69e7f0ba2fdf4894bdc98348370374c3
Source dataset
uspto-grants-2010_07
Patent number
US07750145B2

Reaction notes

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