Table 3.

Syntheses of 3,5-disubstituted hydantoins under dry-grinding (conditions A)^a or PEG-assisted grinding (conditions B and C).^b

Entry	H-AA-OMe	Yields (%)b vs conditionsa			Product
		A	B	C
1	H-Leu-OMe	61 [9]	70	73	2a [9]
2		57 [9]	69	66c	2b [9]
3		38 [9]	n.p.d	48c	2c [9]
4	H-Phe-OMe	84 [9]	70	60	3a [9]
5		30	n.d.e	n.d.e	3b
6		70	n.d.e	n.d.e	3c
7	H-Ser(Ot-Bu)-OMe	51 [9]	70	70	4
8	H-Lys(Z)-OMe	31 [9]	47c	50c	5a [9]
9		62	n.p.d	37c	5b
10		37	n.p.d	n.p.d	5c
11		47	n.p.d	n.p.d	5d
12	H-Aib-OMe	46 [9]	62	62	6 [9]

^aConditions: (step 1) (L)-α-amino ester hydrochloride (1 equiv) and CDI (1.3 equiv) at 450 rpm, in a 12 mL inox jar with 50 balls (stainless steel, 5 mm Ø) for 40 min; (step 2) R²NH₂ (1.6 equiv) and K₂CO₃ (3.6 equiv) at 450 rpm for 2 hours. A: the reaction was performed with no additive (dry-grinding); B: MeO-PEG-2000-OMe (450 mg mmol⁻¹); C: HO-PEG-3400-OH (450 mg mmol⁻¹) were added in the second step (wet-grinding conditions with a PEG additive; ^bisolated yields; ^c1H NMR yield on the crude reaction mixture; ^dthe reaction was not performed (n.p.); ^ethe reaction yield was not determined (n.d.).