. 2014 Sep 18;9(9):e108250. doi: 10.1371/journal.pone.0108250

Table 1. Optimization steps for the synthesis of fentanyl (4); ^aisolated yield; ^balkylation in the synthesis of thiofentanyl derivatives; ^creductive amination.

Entry	Synthetic Step	Reagents/Conditions	T (°C)	Yield^a (%)
1	Alkylation	PhCH₂CH₂Br, Cs₂CO₃, DMF	80	72
2		PhCH₂CH₂Br, Cs₂CO₃, CH₃CN	80	88
3		R-OMs (19), Cs₂CO₃, DMF^b	80	62
4		R-OMs (19), Cs₂CO₃, CH₃CN^b	80	83
5	RA^c	Na(OAc)₃BH, CH₂Cl₂, AcOH	25	91
6		NaCNBH₃, CH₂Cl₂, AcOH	25	64
7		NaBH₄, CH₂Cl₂, AcOH	25	52
8		NaCNBH₃, CH₂Cl₂, AcOH	80	86
9		NaBH₄, CH₂Cl₂, AcOH	80	84
10	Acylation	Propanoyl anhydride, pyridine	25	94
11		Propanoyl chloride, pyridine	25	95
12		Propanoyl chloride, DIPEA, CH₂Cl₂	25	95

Table 1. Optimization steps for the synthesis of fentanyl (4); aisolated yield; balkylation in the synthesis of thiofentanyl derivatives; creductive amination.