2,3-Dihydro-1-benzofuran-5-carbonyl chloride → 4-chloro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)indol-3-yl 2,3-dihydrobenzo[b]furan-5-yl ketone

HRID 544881Notes

Reaction equation

HRID 544881 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15].[O:34]1[CH2:38][CH2:37][C:36]2[CH:39]=[C:40]([C:43](Cl)=[O:44])[CH:41]=[CH:42][C:35]1=2.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[O:34]1[CH2:38][CH2:37][C:36]2[CH:39]=[C:40]([C:43]([C:4]3[C:3]4[C:7](=[CH:8][CH:9]=[CH:10][C:2]=4[Cl:1])[N:6]([C@@H:11]4[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]4[O:13][C:14](=[O:16])[CH3:15])[CH:5]=3)=[O:44])[CH:41]=[CH:42][C:35]1=2

Participants

5

Reactant 3

HCID 27761532,3-Dihydro-1-benzofuran-5-carbonyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 670203794-Chloro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)indole

Product 1

HCID 671966594-chloro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)indol-3-yl 2,3-dihydrobenzo[b]furan-5-yl ketoneYield 122%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole (300 mg) obtained in Example 1-(3) and 2,3-dihydro-benzo[b]furan-5-carbonyl chloride (171 mg) were dissolved in dichloromethane (9 ml), and thereto was added aluminum chloride (166 mg) at 0° C. After being stirred at same temperature for 2.5 hours, the mixture was poured into ice-water (50 ml), and extracted with chloroform (30 ml) twice. The combined organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution (10 ml) and dried over magnesium sulfate. The insoluble materials were filtered off, and the filtrate was evaporated under reduced pressure to give crude 4-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl 2,3-dihydrobenzo[b]furan-5-yl ketone (477 mg), which was partially deacetylated. This crude compound was dissolved in chloroform (9 ml), and thereto were added successively pyridine (0.151 ml), acetic anhydride (0.177 ml) and 4-(dimethyl-amino)pyridine (7.6 mg). After being stirred at room temperature for 16 hours, the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (100 ml), and the mixture was washed with a 10% aqueous copper (II) sulfate solution (10 ml) twice and a saturated aqueous sodium hydrogen carbonate solution (10 ml), and dried over magnesium sulfate. The insoluble materials were filtered off, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10-60:40) to give 4-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indol-3-yl 2,3-dihydrobenzo[b]furan-5-yl ketone (346 mg) as a colorless powder. APCI-Mass m/Z 628/630 (M+H). 1H-NMR (DMSO-d6) δ 1.71 (s, 3H), 1.97 (s, 3H), 1.98 (s, 3H), 2.04 (s, 3H), 3.25 (td, J=8.8, 2.2 Hz, 2H), 4.08-4.14 (m, 2H), 4.30 (ddd, J=9.9, 5.3 and 3.0 Hz, 1H), 4.66 (t, J=8.8 Hz, 2H), 5.28 (t, J=9.8 Hz, 1H), 5.54 (t, J=9.6 Hz, 1H), 5.72 (t, J=9.4 Hz, 1H), 6.32 (d, J=9.0 Hz, 1H), 6.87 (d, J=8.3 Hz, 1H), 7.25 (d, J=7.7 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 7.64 (dd, J=8.3, 1.6 Hz, 1H), 7.72 (br, 1H), 7.78 (d, J=8.3 Hz, 1H), 8.03 (s, 1H).

Workup

  1. extractionextracted with chloroform (30 ml) twice
  2. washThe combined organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution (10 ml)
  3. dry with materialdried over magnesium sulfate
  4. filtrationThe insoluble materials were filtered off
  5. customthe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-fd0ff1fa87354eb5aaaab2f8840528c0
Source dataset
uspto-grants-2011_05
Patent number
US07935674B2

Reaction notes

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