J
D. J. Modemann et al.
Feature
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C23H35INO6+: 548.15035; found:
548.15100; m/z [M + Na]+ calcd for C23H34INNaO6+: 570.13229; found:
570.13289; m/z [M + K]+ calcd for C23H34IKNO6+: 586.10623; found:
586.10690.
1H NMR (600 MHz, CDCl3): δ = 7.53 (t, J = 7.3 Hz, 1 H), 7.49 (t, J =
7.3 Hz, 1 H), 7.40 (dd, J = 23.1, 8.2 Hz, 1 H), 7.17 (t, J = 8.1 Hz, 1 H),
7.09 (s, 2 H), 4.87–4.62 (m, 2 H), 4.40–4.20 (m, 1 H), 4.20–3.96 (m,
1 H), 3.78 (dd, J = 13.5, 9.5 Hz, 1 H), 3.63 (dd, J = 14.3, 8.0 Hz, 1 H),
3.37 (s, 1 H), 3.25 (s, 2 H), 2.64–2.57 (m, 6 H), 2.33 (s, 3 H), 1.64–1.56
(m, 6 H), 1.48–1.43 (m, 12 H).
13C NMR (151 MHz, CDCl3): δ = 170.5, 170.1, 154.4, 154.2, 144.4,
144.3, 142.5, 142.2, 141.2, 140.9, 134.0, 134.0, 132.4, 132.4, 132.3,
132.1, 130.7, 130.5, 130.4, 121.3, 120.4, 118.4, 118.3, 84.3, 83.6, 82.9,
81.8, 80.0, 79.4, 61.6, 60.4, 56.1, 55.9, 40.9, 39.6, 28.5, 28.2, 28.0, 27.9,
27.0, 21.1.
4-{2-[(2S)-2-{Bis[(tert-butoxy)carbonyl]amino}-3-(tert-butoxy)-3-
oxopropyl]phenyl}(2,4,6-trimethylphenyl)iodanium Tetrafluo-
roborate (10)
Compound 10 was prepared as described for 6·BF4 using 9 (0.32 g,
0.58 mmol), TMSOAc (0.23 mL, 1.51 mmol), SelectfluorTM (0.26 g, 0.75
mmol) and MesBF3K (0.13 g, 0.58 mmol). The crude product was puri-
fied by flash chromatography (0–10%, MeOH/CH2Cl2).
19F NMR (565 MHz, CDCl3): δ = –149.91, –149.97.
HRMS (ESI): m/z [M–BF4–]+ calcd for C29H41INO5+: 610.20184; found:
Yield: 0.39 g (89%); colorless solid; Rf 0.5 (10%, MeOH/CH2Cl2).
1H NMR (600 MHz, CDCl3): δ = 7.57 (d, J = 8.5 Hz, 2 H), 7.29 (d, J =
8.5 Hz, 2 H), 7.13 (s, 2 H), 4.97 (dd, J = 9.5, 5.5 Hz, 1 H), 3.42 (dd, J =
14.4, 5.5 Hz, 1 H), 3.17 (dd, J = 14.4, 9.5 Hz, 1 H), 2.62 (s, 5 H), 2.38 (s,
3 H), 1.43 (2 s, J = 9.2 Hz, 9 H), 1.41 (s, 18 H).
13C NMR (151 MHz, CDCl3): δ = 168.9, 152.3, 145.3, 144.1, 143.0,
134.0, 132.9, 130.9, 118.9, 107.9, 83.5, 82.27, 59.5, 35.6, 28.1, 28.1,
27.4, 21.3.
610.20222.
{2-[(2S)-2-{Bis[(tert-butoxy)carbonyl]amino}-3-(tert-butoxy)-3-
oxopropyl]phenyl}(2,4,6-trimethylphenyl)iodanium p-Tosylate
(6·TsO)
A solution of 6·BF4 (0.10 g, 0.13 mmol) in MeOH was passed through a
column filled with AG1-X8 (in TsO– form, 100–200 mesh). The solu-
tion was concentrated under reduced pressure to afford 6·TsO.
19F NMR (565 MHz, CDCl3): δ = –147.92, –147.97.
Yield: 0.11 g (>99%); colorless solid; Rf 0.6 (10%, MeOH/CH2Cl2).
HRMS (ESI): m/z [M–BF4–]+ calcd for C32H45INO6+: 666.22805; found:
666.22837.
1H NMR (600 MHz, CDCl3): δ = 7.49 (d, J = 8.0 Hz, 2 H), 7.45–7.37 (m,
2 H), 7.35 (d, J = 8.1 Hz, 1 H), 7.11–7.05 (m, 1 H), 6.99 (d, J = 7.9 Hz,
2 H), 6.95 (s, 2 H), 4.98–4.92 (m, 1 H), 3.64 (dd, J = 14.1, 8.0 Hz, 1 H),
3.30 (dd, J = 14.2, 6.3 Hz, 1 H), 2.61 (s, 6 H), 2.29 (2s, 6 H), 1.49 (s,
18 H), 1.45 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 169.1, 152.4, 143.3, 143.2, 142.0,
140.9, 138.9, 134.2, 132.4, 131.7, 130.1, 130.0, 128.3, 126.1, 124.7,
119.4, 84.0, 83.3, 59.4, 39.3, 28.2, 28.1, 27.2, 21.4, 21.2.
Boc(MOM)-2-IPhe-OtBu (11)
The reaction was performed as described by Barnes et al.17 TMSCl
(0.39 mL, 3.09 mmol) was added to an ice-cold solution of 2 (0.46 g,
1.03 mmol) and paraformaldehyde (0.05 g, 1.54 mmol) in CH2Cl2 (10
mL) and the reaction mixture was stirred for 5 h. The mixture was
then warmed to ambient temperature, a solution of Et3N (0.3 mL) in
MeOH (2.7 mL) was added, and the reaction mixture was stirred for 1
h. 10% NaHCO3 (15 mL) was added and the resulting emulsion was ex-
tracted with CH2Cl2 (×3). The combined organic fractions were dried,
concentrated under reduced pressure, and the residue was purified by
flash chromatography (5%, EtOAc/hexane) to afford 11.
19F NMR (565 MHz, CDCl3): no signals.
HRMS (ESI): m/z [M–BF4–]+ calcd for C32H45INO6+: 666.22805; found:
666.22835.
Radiochemistry
Yield: 0.40 g (79%); colorless oil; Rf 0.3 (10%, EtOAc/hexane).
All radiosyntheses were carried out using anhydrous DMF (Aldrich).
(MeCN)4CuOTf (Aldrich) was stored under argon. QMA cartridges
(Sep-Pak Accell Plus QMA Carbonate Plus Light Cartridge) were ob-
tained from Waters (Waters GmbH, Eschborn, Germany) and used
without preconditioning, unless otherwise noted. RP-cartridges
(Strata™-X 33 μm polymeric reversed phase, 200 mg/3 mL, tube)
were from Phenomenex (Phenomenex Ltd., Aschaffenburg, Germany).
1H NMR (600 MHz, CDCl3): δ = 7.84–7.76 (m, 1 H), 7.23 (dd, J = 13.7,
6.9 Hz, 1 H), 7.18–7.12 (m, 1 H), 6.90 (dd, J = 15.1, 7.5 Hz, 1 H), 4.69 (d,
J = 10.8 Hz, 0.5 H), 4.50 (d, J = 11.2 Hz, 0.5 H), 4.39–4.28 (m, 0.5 H),
4.23 (dd, J = 10.8, 4.8 Hz, 0.5 H), 3.95 (d, J = 10.2 Hz, 0.5 H), 3.82 (d, J =
11.2 Hz, 0.5 H), 3.53–3.38 (m, 1.5 H), 3.32–3.24 (m, 0.5 H), 3.17 (s,
1.5 H), 3.11 (s, 1.5 H), 1.49 (2s, 18 H).
13C NMR (151 MHz, CDCl3, two rotamers were observed): δ = 169.86,
169.64, 155.31, 154.41, 141.51, 141.00, 139.71, 139.57, 131.41,
131.26, 128.62, 128.46, 128.31, 100.75, 81.79, 81.59, 81.38, 80.77,
80.12, 79.65, 59.31, 59.19, 56.15, 55.71, 40.84, 39.90, 28.50, 28.46,
28.26, 28.14.
[
18F]Fluoride was produced by the 18O(p,n)18F reaction by bombard-
ment of enriched [18O]water with 16.5 MeV protons using a BC1710
cyclotron (The Japan Steel Works Ltd., Shinagawa, Japan) at the INM-5
(Forschungszentrum Jülich). All radiolabeling experiments were car-
ried out under ambient or synthetic air.
HRMS (ESI): m/z [M + Na]+ calcd for C20H30INNaO5+: 514.10664;
found: 514.10631.
Each radiochemical experiment was carried out at least in triplicate if
not otherwise mentioned.
(S)-2-{(3-tert-Butoxy)-2-[(tert-butoxycarbonyl)(methoxymeth-
yl)amino]-3-oxopropyl}phenyl(mesityl)iodonium Tetrafluorobo-
rate (12)
HPLC Analysis
Before the determination of radiochemical conversions (RCCs), reac-
tion mixtures were diluted with H2O (1–4 mL) (or 50% MeOH) to dis-
solve any 18F-fluoride adsorbed onto the reaction vessel walls. The
loss of radioactivity on the vessel walls did not exceed 13±2% from
the starting activity (n > 100). All radiochemical yields (RCYs) were
decay corrected and radiochemical purities (RCPs) were determined
after purification.
Compound 12 was prepared as described for 6·BF4 from 11 (0.37 g,
0.75 mmol) using TMSOAc (0.29 mL, 1.96 mmol), SelectfluorTM (0.35
g, 0.98 mmol) and MesBF3K (0.17 g, 0.75 mmol). The crude product
was purified by flash chromatography (0–10% MeOH in CH2Cl2).
Yield: 0.41 g (78%); colorless solid; Rf 0.6 (10%, MeOH/CH2Cl2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M