Amide bond formation using an air-stable source of AlMe3

Novak, Andrew; Humphreys, Luke; Walker, Matthew; Woodward, Simon

doi:10.1016/j.tetlet.2006.06.004

Cited by 54 publications

(31 citation statements)

References 13 publications

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“…DABAL-Me 3 amide formation has been reported to proceed slowly in refluxing THF under conventional heating (CH), such as isomantles or oil baths, [3] but much more rapidly when microwave heating (MWH) is used. [4] In previous reports, we had recommended the use of 0.8 equivalents of DABAL-Me 3 per equivalent of a 1:1 methyl ester:amine mixture at 0.25 M in THF.…”

Section: Comparison Of Heating Methods Solvents and Scalesmentioning

confidence: 99%

“…Over 300 such 'coupling agents' are described in key reviews covering this area [2] and some of the more commonly used species are shown in Scheme 1. In 2006 [3] and 2008 [4] we provided preliminary details of the use of DABCO·(AlMe 3 ) 2 (which we call DABAL-Me 3 ) in such rolesbased on the seminal direct coupling of RCO 2 Me and amines using AlMe 3 by Weinreb. [5] Recently, related AlMe 3 alone couplings of free carboxylic acids and amines have also appeared.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard it is insightful to initially compare the reagents of Scheme 1 in a hypothetical R (Table 1). It might be suggested, based on Table 1, that AlMe 3 -based 'coupling agents' [3][4]6] are: mid-cost, rather too active for peptide coupling, uniquely able to use both free carboxylic acids and their esters (see later), but of significant utility for formation of tert-amides. This present paper attempts to provide comprehensive answers to the questions (i)-(v) posed above and thus more fully define the scope and limitations of these DABAL-Me 3 promoted couplings.…”

Section: Introductionmentioning

confidence: 99%

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On DABAL-Me3 promoted formation of amides

et al. 2013

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Abstract. The range and utility of DABAL-Me 3 couplings of methyl esters and free carboxylic acids with primary and secondary amines under a variety of conditions (reflux, sealed tube, microwave) has been compared for a significant range of coupling partners of relevance to the preparation of amides of interest in pharmaceutical chemistry. Commercial microwave reactors promote the fastest couplings and allow the use of significantly sterically hindered amines (primary and secondary) and carboxylic acids derivatives. The influence of microwave energy on the reaction system was shown to be typically related to thermal effects (over-pressuring and superheating).

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Section: Comparison Of Heating Methods Solvents and Scalesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On DABAL-Me3 promoted formation of amides

et al. 2013

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“…N-(4-Methyl-3-(phenylamino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide (4). To a large flame-dried Schlenk tube (60 mm diameter × 300 mm length, internal volume = 550 mL) was added DABAL-Me 3 1 (13.45 g, 52.5 mmol), amine 8 (13 g, 65.6 mmol), and ester 5 (16.3 g, 65.6 mmol).…”

Section: ■ Conclusionmentioning

confidence: 99%

Investigating Scale-Up and Further Applications of DABAL-Me₃ Promoted Amide Synthesis

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Amara

Poliakoff

et al. 2015

Org. Process Res. Dev.

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Methods for the batch scale up of DABAL-Me 3 promoted direct ester to amide synthesis have been demonstrated at 10−100 g scales using a tert-amide model compound. Procedures for 20 g scale couplings in standard laboratory glassware and up to 0.1 kg in industry-standard jacketed glass reactors in near quantitative yields are given. A derivative of the anticancer agent Imatinib (Gleevec) has been synthesized on a 26 g scale (98% yield, >98% purity) establishing DABAL-Me 3 as a potential alternative for the synthesis of amides in API scale preparations. Continuous flow methodology provides a method for larger scales (productivities of >50 g h −1 ). In addition, nitriles were coupled to primary amines and hydrazines with DABAL-Me 3 , resulting in the clean formation of free amidines (16 examples) and amidrazones.

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“…5 (D) Direct formation of amides from the corresponding inactivated esters and lactones can be conveniently carried out with DABALMe 3 excluding the risk of using other pyrophoric AlR 3 reagents. 6 Woodward and co-workers later utilized microwave irradiation in DABAL-Me 3 -mediated amide bond formation in order to carry out the reaction in a shorter span of time. 7 …”

Section: Abstractsmentioning

confidence: 99%