1-Bromo-3-chloropropane → HCID 66885972, compound

HRID 2353023Notes

Reaction equation

HRID 2353023 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@@H:20]3[O:46][C@H:45]([CH2:47][O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41])[C@H:29]([O:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C@H:21]3[O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:12]=[CH:11]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:62][CH2:63][CH2:64][Cl:65]>CC(C)=O>[Cl:65][CH2:64][CH2:63][CH2:62][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@@H:20]3[O:46][C@H:45]([CH2:47][O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:41])([CH3:42])[CH3:43])[C@H:29]([O:30][C:31](=[O:36])[C:32]([CH3:33])([CH3:34])[CH3:35])[C@H:21]3[O:22][C:23](=[O:28])[C:24]([CH3:26])([CH3:27])[CH3:25])[CH:12]=[CH:11]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 10796Cesium carbonateHCID 57584217HCID 57584217, compound

Product 1

HCID 66885972HCID 66885972, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 1-[2-(4-hydroxyphenyl)ethyl]-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (0.2 g), cesium carbonate (0.17 g) and 1-bromo-3-chloropropane (0.05 mL) in acetone (4 mL) was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1) to give 1-{2-[4-(3-chloropropoxy)phenyl]ethyl}-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (0.21 g). This material was dissolved in acetonitrile (6 mL). To the solution was added sodium iodide (46 mg), and the mixture was heated for reflux overnight. To the reaction mixture were added tris(hydroxymethyl)aminomethane (0.31 g) and ethanol (4 mL), and the mixture was stirred at 60° C. for 2 days. The reaction mixture was purified by column chromatography on aminopropylated silica gel (eluent: methylene chloride/methanol=30/1-5/1) to give 1-[2-(4-{3-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl-amino]propoxy}phenyl)ethyl]-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (0.13 g). This material was dissolved in methanol (3 mL). To the solution were added water (0.3 mL) and lithium hydroxide monohydrate (24 mg), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction method on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (71 mg).

Workup

  1. customThe reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1)

Sources & evidence

ORD record
ord-7a87b020a22c4f408efab1caf7b4fccb
Source dataset
uspto-grants-2010_07
Patent number
US07749972B2

Reaction notes

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