A kind of s-type 3-hydroxyl-3-alkynyl oxidindole compound and its synthesis method and application
A technology of indole oxide and synthesis method, applied in the directions of organic chemistry method, chemical instrument and method, asymmetric synthesis, etc., to achieve the effects of easy availability of raw materials, mild reaction conditions and simple operation
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0038] The present invention also provides a synthetic method of S-type 3-hydroxyl-3-alkynyl oxindole compounds shown in general structural formula (I), said synthetic method comprising the following steps:
[0039] (1) in N 2 Under protection, respectively add metal copper salt, chiral ligand, and organic solvent into the reaction device, and stir for 0.5 to 2 hours, so that the copper salt and the chiral ligand are fully complexed;
[0040] (2) After fully complexing, add the isatin compound, terminal alkyne compound, organic base and the organic solvent respectively, and then place the reaction device in a heating device to heat the reaction, and the reaction temperature is 0-100°C , to react for several hours;
[0041] (3) After the reaction is complete, the compound shown in general structural formula (I) is obtained through post-treatment.
[0042] The post-treatment is as follows: filter through diatomaceous earth, remove the solvent, and then separate the mixture thr...
Embodiment 1
[0045] Synthesis of (S)-1-benzyl-3-hydroxyl-3-(phenylethynyl)-7-trifluoromethyloxindole (compound 1), whose structural formula is:
[0046]
[0047] Preparation method 1: Under nitrogen protection, add 1.9 mg of cuprous iodide, 7.1 mg of (S)-N-((1R,2R)-2-(diphenylphosphino)-cyclohexyl Alkyl)-2-((4-methylphenyl)sulfonamido)-3-phenylpropanamide, 0.5mL methyl tert-butyl ether, stir well for 30 minutes, then add 61.1mg 1-benzyl-7-trifluoromethyl isatin, 21.4mg phenylacetylene, 40.5mg triethylamine and 0.5mL methyl tert-butyl ether were placed in an oil bath at 40°C for 72 hours, and finally subjected to conventional Workup gave 76.6 mg of compound 1 with a yield of 94% and an enantioselectivity of 92% ee(S).
[0048] Preparation method 2: Under nitrogen protection, add 1.9 mg cuprous iodide, 6.8 mg (S)-N-((1R,2R)-2-(diphenylphosphino)-cyclohexyl Alkyl)-2-((4-methylphenyl)sulfonamido)-2-phenylacetamide, 0.5mL methyl tert-butyl ether, stir and complex for 30 minutes, then add 6...
Embodiment 2
[0057] Synthesis of (S)-1-(4-methylbenzyl)-3-hydroxyl-3-(phenylethynyl)-7-trifluoromethyloxindole (compound 2), whose structural formula is:
[0058]
[0059] Under nitrogen protection, 1.9 mg of cuprous iodide, 7.1 mg of (S)-N-((1R,2R)-2-(diphenylphosphino)-cyclohexyl)- 2-((4-Methylphenyl)sulfonamido)-3-phenylpropanamide, 0.5mL methyl tert-butyl ether, stir well for complexation for 1 hour, then add 63.9mg 1-(4- Methylbenzyl)-7-trifluoromethylisatin, 21.4mg phenylacetylene, 40.5mg triethylamine and 0.5mL methyl tert-butyl ether were placed in an oil bath at 40°C for 72 hours, and finally Conventional workup afforded 75.9 mg of compound 2 in 90% yield and enantioselectivity of 91% ee(S).
[0060] Compound 2 has a melting point of 147-148°C.
[0061] The NMR characterization results of compound 2 are: 1 H NMR (400MHz, CDCl 3 ):δ7.84(d,J=7.3Hz,1H),7.61(d,J=7.7Hz,1H),7.45-7.37(m,2H),7.35-7.19(m,4H),7.09-7.00( m,4H),5.17(s,2H),4.40(brs,1H),2.27(s,3H); 13 C NMR (100MHz, CD...
PUM
| Property | Measurement | Unit |
|---|---|---|
| melting point | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More