Table 1.

Optimisation experiments for S_NAr with ethyl cyanoacetate (10).^a

Entry	9 [M]	10 (equiv)	Solventb	Basec (equiv)	Temp. (°C)	% Conv.
1	0.25	2	MeCN	Et3N (5)	50	8
2	0.25	2	DCM	Et3N (5)	40	3
3	0.25	2	DMF	Et3N (5)	70	6
4	0.5	2	DMF	TMG (3)	40	98
5	0.75	2	DMF	TMG (3)	40	100d
6	0.25	1	DMF	TMG (3)	40	88
7	0.25	2	DCM	TMG (3)	40	100
8	0.25	2	EtOH	NaOEt (3)	40	–e
9	0.25	2	t-BuOH	KOt-Bu	40	44d
10	0.25	2	DMF	K2CO3 (5)	40	100d
11	0.25	2	THF	TMG (3)	50	55d
12	0.25	2	EtOAc	TMG (3)	50	90d
13	0.25	2	EtOAc/MeCN 5:1	TMG (2.5)	50	>98
14	0.25	2	EtOH	TMG (3)	50	64
15	0.25	2	MeCN	TMG (3)	50	100
16	0.25	1	MeCN	TMG (3)	50	90
17	0.25	1.5	MeCN	TMG (3)	50	100
18	0.25	1.2	MeCN	TMG (3)	50	100
19	0.25	1.1	MeCN	TMG (3)	50	100
20	0.25	1.1	MeCN	TMG (2)	50	87
21	0.25	1.1	MeCN	TMG (2.2)	50	94
22	0.25	1.1	MeCN	TMG (2.5)	50	100
23	0.25	1.1	MeCN	TMG (2.5)	40	96
24	0.25	1.1	DCM	TMG (2.5)	50	100
25	0.25	1.1	DCM	TMG (2.5)	40	89
26	0.5	1.1	DMF	TMG (2.5)	50	100
27	0.25	2	EtOAc/MeCN 5:1	TMG (2.5)	50	100

^aAll reactions were run in Biotage microwave vials being irradiated at the specified temperature for 1 hour. The organic phase was analysed after work-up by quenching with 1 M HCl (and extraction with EtOAc if required), drying over anhydrous Na₂SO₄ and solvent evaporation. Conversion to product was based upon calibrated LC. ^bSolvents were tested for full solubility of reagents and for the deprotonated ethyl cyanoacetate (10) prior to full testing. ^cIt was determined that DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and TMG (1,1,3,3-tetramethylguanidine) could be used interchangeably without any effect on the yield or product purity, for clarity only the results with TMG are shown. ^dSolid formation occurred during the reaction. ^eComplex mixture generated including direct addition of the ethoxide anion.