Fluorination of silyl prosthetic groups by fluorine mediated silyl ether linker cleavage: a concept study with conditions applicable in radiofluorination

EJNMMI Radiopharmacy and Chemistry

Table 1 Detagging conditions of silyl ethers 5, 6, and 9

Entry	Linker	Cleavage conditions	Result (HPLC analysis)
1	Diethylenglycol	KF, K₂CO₃, Kryptofix®222, rt, THF, 10 min	Silanol (major) Fluoride 7 (minor)
2	NovaSyn® TG hydroxy resin	KF, K₂CO₃, Kryptofix®222, rt, THF, 10 min	Silanol (pure)
3	PEG linker NovaSyn® TG hydroxy resin	KF, K₂CO₃, Kryptofix®222 (note: pre-drying of fluorination reagents by three times co-evaporation with ACN at 120 °C under vacuum), then reaction at 55 °C, THF, 30 min	Silanol (pure)
4	PEG linker NovaSyn® TG hydroxy resin	Pre-drying of solid phase, KF, K₂CO₃, Kryptofix®222, rt, 8 min	Silanol (pure)
5	2-(2-aminoethoxy)ethanol	Pre-drying of solid phase, KF, K₂CO₃, Kryptofix®222, rt, 7 min	Fluoride 7 (pure)
6	2-(2-aminoethoxy)ethanol	CsF, K₂CO₃, Kryptofix®222 (all reagents pre-dried), rt, ACN, 30 min	Silanol (major) Fluoride 7 (traces)
7	2-(2-aminoethoxy)ethanol	KF, K₂CO₃, 18-crown-6, THF, rt, 10 min	Fluoride 7 (major) Silanol (minor)
8	2-(2-aminoethoxy)ethanol	TBAF, THF, rt, 2 h	Silanol (pure)
9	2-(2-aminoethoxy)ethanol	Olah’s reagent, THF, 0 °C, 8 h	Fluoride 7 (pure)
10	2-(2-aminoethoxy)ethanol	Pre-drying of solid phase, KF, K₂CO₃, Kryptofix®222, rt, 8 min	Fluoride 7 (pure) (semiquantitative scale) (56% overall yield over 3 steps)