Table 1.

Amide- or ester-forming reactions in water media.

entry	additive / solvent	7 or 8	product (10 or 11)	yield (%)d
1a	5b H2O	HCl•H-L-Ala- OMe(7a)	Boc-Phe-Ala- OMe (10a)c	93
2a	5a H2O	7a	10ac	25
3b	5b H2O	MeOH	Boc-Phe-OMe (11a)c	45
4b	5b 50% H2O- CH3CN	MeOH	11a	55
5b	5b 5%H2O- CH3CN	MeOH	11ac	>95
6b	5a 5%H2O- CH3CN	MeOH	11ac	>95
7b	5a 5%H2O- dioxane	MeOH	11ac	90
8b	5a 5%H2O- acetone	MeOH	11ac	85
9b	5a 5%H2O- CH3CN	iPrOH	Boc-Phe-OiPr (11b)c	0
10b	5a 5%H2O- CH3CN	tBuOH	Boc-Phe-OtBu (11c)c	0

^a6 (1.0 equiv), 7 (1.5 equiv), additive (1.5 equiv), EDCI (1.5 equiv), NaHCO₃ (6 equiv) in H₂O (0.2 M concentrations), 2 h;

^b6 (1.0 equiv), 8 (2.0 equiv), additive (1.5 equiv), EDCI (1.5 equiv), NaHCO₃ (6 equiv) (0.2 M concentrations);

^cde or ee was determined to be >99% via HPLC analysis;

^disolated yield.