90% |
With thionyl chloride In dichloromethane for 24h; Ambient temperature; |
|
80% |
With thionyl chloride In dichloromethane at 20℃; for 2h; |
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With thionyl chloride In dichloromethane for 0.5h; Heating; Yield given; |
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With pyridine; thionyl chloride In dichloromethane Heating; |
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With thionyl chloride In dichloromethane at 20℃; for 24h; |
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With 2,4,6-trimethyl-pyridine; bis(trichloromethyl) carbonate In tetrahydrofuran at 0℃; Inert atmosphere; |
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With thionyl chloride In tetrahydrofuran at 20℃; |
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With thionyl chloride In dichloromethane for 2h; Inert atmosphere; Reflux; |
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With thionyl chloride In dichloromethane for 0.5h; Sonication; |
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 2h; Reflux; |
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With thionyl chloride In dichloromethane at 20℃; Inert atmosphere; Sonication; |
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; |
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With thionyl chloride In dichloromethane |
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With thionyl chloride In dichloromethane at 40℃; for 0.5h; |
15.1
SOCI2 (7.28 ml, 0.120 mol) was added to a suspension of Fmoc-Phe-OH 5 (7.74 g, 0.020 mol) in CH2CI2 (100 ml) and N,N-Dimethylformadide (2 drops, catalytic). The EPO reaction mixture was warmed at 40 0C for.30 minutes. The course of the reaction was monitored by adding MeOH to a sample of the reaction mixture to detect the formation of the corresponding methyl ester. Upon completion, 2 drops of toluene was added to the reaction mixture and the solvent was removed under vacuum. The residue was used immediately for the next reaction. |
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With oxalyl dichloride; 3,3-dichloro-1,2-diphenylcyclopropene; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere; |
Preparation of Weinreb amides (2a-d) and (5a-h)
General procedure: To a solution of in situ generated CPI-Cl (generated by the treatment of 2,3 diphenylcyclopropenone (1.1 mmol) with oxalyl chloride (1 mmol) in Cl2Cl2) was added aryl/heterocyclic/Nα-protected amino acid (1 mmol), DIPEA (2 mmol) stirring at room temperature. After the formation of acid chloride solution of N,O-dimethylhydroxylamine (2 mmol) in CH 2 Cl 2 was added. After the completion of the reaction (determined by TLC), solvent was evaporated under vacuo and diluted with EtOAc, washed with 5% citric acid (10 mL x 2) and Na 2 CO 3 (10 mL x 2), water, brine and dried over anhydrous Na 2 SO 4 . After filteration, solvent was evaporated and purified by column chromatography using hexane and EtOAc as eluents. |
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With 3,3-dichloro-1,2-diphenylcyclopropene; N-ethyl-N,N-diisopropylamine In dichloromethane at -10 - 20℃; for 0.166667h; |
General procedure for the synthesis of Nα-protected amino hydroxamic acid.
General procedure: To a solution of 3,3-dichloro-1,2-diphenylcyclopropene at -10 oC [1.1 equiv. prepared by adding diphenylcyclopropenone (1.0 equiv.) in DCM and oxalyl chloride (1.0 equiv.) at rt and stirred until the gas evolution has ceased] was added a solution of Nα-protected amino acid (1.0 equiv.) and diisopropylethylamine (1.2 equiv.) in dichloromethane and stirred. After 10 min hydroxylamine hydrochloride (NH2OH.HCl, 1.5 equiv.) in methanolic potassium hydroxide was added to the reaction mixture and stirred of another 45 min. The solvent was removed under reduced pressure; the residue obtained was diluted with EtOAc, washed with 10% citric acid solution, water and brine solution. The organic phase was dried over anhydrous Na2SO4 and removed under reduced pressure. The crude residue was purified by column chromatography using n-hexane and ethyl acetate as eluents. |
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With thionyl chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Sonication; |
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With thionyl chloride In dichloromethane Sonication; |
2.1. Brief Procedure for the Preparation of AminoacylChloride
General procedure: In a 50 mL round bottomed flask, N-Fmoc-protectedamino acid (1mmol), dichloromethane (CH2Cl2) 6 mL andfreshly distilled thionyl chloride (1.2 mmol) was added andthe mixture was sonicated till the reaction completion, thereaction was monitored by TLC. After reaction, the excessof thionyl chloride and DCM were removed under vacuum,followed by addition of hexane separates solid product, itwas filtered and dried under vacuum taken directly for thereaction for the reaction [49]. |