Table 1.

Microflow amide bond formation with various solvents and bases.^[a]

Entry	Solvent	Base	Yield [%]
	A	B	C		3	4
1	CH2Cl2	CH2Cl2	CH2Cl2	DIEA	31	1
2	1,4-dioxane	1,4-dioxane	1,4-dioxane	DIEA	–[b]	–
3	MeCN	MeCN	MeCN	DIEA	48	2
4	iPrOH	MeCN	MeCN	DIEA	–[c]	–
5	MeCN	MeCN	MeCN/H2O (1:1)	DIEA	52	3
6	NMP	MeCN	MeCN	DIEA	<55	<10
7	DMF	MeCN	MeCN	DIEA	62	9
8	MeCN/H2O (9:1)	MeCN	MeCN	DIEA	56	15
9	MeCN/DMF (9:1)	MeCN	MeCN	DIEA	55	2
10	DMF/H2O (9:1)	MeCN	MeCN	DIEA	58	9
11	DMF	MeCN	MeCN	Et3N	–[b]	–
12	DMF	MeCN	MeCN	Me2NEt	52	10
13	DMF	MeCN	MeCN	Cy2NMe	63	15
14	DMF	MeCN	MeCN	lutidine	48	1
15	DMF	MeCN	MeCN	collidine	–[b]	–
16	DMF	MeCN	MeCN	DBU	24	9
17	DMF	MeCN	MeCN	DABCO	–[b]	–
18	H2O	MeCN	MeCN	LiOH	–[b]	–

^[a]Flow rate A: 2000 μL min⁻¹, flow rate B: 1200 μL min⁻¹, flow rate C: 2000 μL min⁻¹.

^[b]Insoluble salts were generated.

^[c]A complex mixture was obtained. Boc=tert-butoxycarbonyl, DABCO=1,4-diazabicyclo[2,2,2]octane, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DIEA=N,N-diisopropylethylamine, DMF=N,N-dimethylformamide, NMP=N-methylpyrrolidone.