S.D. Nielsen et al. / Tetrahedron 67 (2011) 5261e5267
5265
(d, J¼8.0 Hz, 2H), 7.36 (d, J¼8.0 Hz, 2H); 13C NMR
d
24.3, 24.4, 26.2,
d
25.4, 31.2 (t, J¼22 Hz), 34.7, 74.1, 128.5, 129.6, 131.8, 140.0; HRMS
28.3, 32.9 (t, J¼22 Hz), 40.6, 49.0, 67.6, 76.6, 81.4, 114.9, 117.1, 122.8,
123.8, 128.4, 129.9, 134.0, 139.5, 145.4, 156.5, 164.2; HRMS calcd for
C29H26F17N2O3þ, 773.1666 (eBocþ, þHþ); found 773.1674.
calcd for C18H15F17NOþ, 584.0877 (þHþ); found 584.0855.
4.3.2. N-(3-(10H-phenothiazin-10-yl)propyl)-O-(4-(2-perfluoroctyl-
ethyl)benzyl)hydroxylamine hydrochloride (3c). Prepared by general
procedure B to give 791 mg (99%) of 3c as a grey solid. Purity by
4.2.5. tert-Butyl 4-methylbenzyl(4-(2-perfluoroctylethyl)benzyloxy)
carbamate (2e). Prepared by general procedure A to give 1.73 g
(100%) of 2e as a white solid. Purity by LCeUV(ELS)¼100%(100%);
LCeUV(ELS)¼91%(nd); 1H NMR (CD3OD)
d 2.19e2.26 (m, 2H),
2.42e2.55 (m, 2H), 2.94e3.00 (m, 2H), 3.43e3.48 (m, 2H), 4.13 (t,
J¼6.2 Hz, 2H), 4.95 (s, 2H), 6.96e7.00 (m, 2H), 7.03e7.06 (m, 2H),
7.17e7.24 (m, 4H), 7.28 (d, J¼8.0 Hz, 2H), 7.3 (d, J¼8.0 Hz, 2H); 13C
1H NMR
d 1.50 (s, 9H), 2.28e2.40 (m, 5H), 2.87e2.92 (m, 2H), 4.52
(s, 2H), 4.65 (s, 2H), 7.12e7.18 (m, 4H), 7.21e7.25 (m, 4H); 13C NMR
d
21.08, 26.2, 28.3, 32.9 (t, J¼22 Hz), 53.6, 76.9, 81.5, 128.2, 128.7,
NMR (CD3OD)
d
22.5, 27.1, 33.4 (t, J¼22 Hz), 44.9, 48.2, 76.8,
129.0, 129.9, 133.9, 134.1, 137.2, 139.4, 156.7; HRMS calcd for
106e121 (8 fluorinated carbon), 117.2, 124.2, 127.5, 128.6, 128.7,
130.1, 130.9, 132.3, 142.5, 146.4; HRMS calcd for C32H26F17N2OSþ,
809.1489 (þHþ); found 809.1473.
C26H21F17NO3þ, 718.1244 (etBuþ, þHþ); found 718.1268.
4.2.6. tert-Butyl isopentyl(4-(2-perfluoroctylethyl)benzyloxy)carba-
mate (2f). Prepared by general procedure A to give 3.19 g (99%) of
2f as a colourless oil. Purity by LCeUV(ELS)¼100%(100%); 1H NMR
4.3.3. 4-(4-(((4-(2-Perfluoroctylethyl)benzyl)oxy)amino)butyl)-2H-
benzo[b][1,4]oxazin-3(4H)-one hydrochloride (3d). Prepared by
general procedure B to give 1.22 g (99%) of 3d as a white solid.
d
0.89 (d, J¼6.6 Hz, 6H), 1.45e1.63 (m, 12H), 2.29e2.42 (m, 2H),
2.89e2.95 (m, 2H), 3.42 (t, J¼7.5 Hz, 2H), 4.81 (s, 2H), 7.21 (d,
Purity by LCeUV(ELS)¼100%(100%); 1H NMR (CD3OD)
d 1.77e1.81
J¼7.8 Hz, 2H), 7.37 (d, J¼7.8 Hz, 2H); 13C NMR
d
22.4, 25.7, 26.2, 28.3,
(m, 4H), 2.42e2.55 (m, 2H), 2.95e3.00 (m, 2H), 3.36e3.44 (m, 2H),
4.03e4.09 (2 m, H), 4.59 (s, 2H), 5.07 (s, 2H), 6.99e7.10 (m, 3H),
7.18e7.22 (m, 1H), 7.36 (d, J¼8.0 Hz, 2H), 7.41 (d, J¼8.0 Hz, 2H); 13C
32.9 (t, J¼22 Hz), 35.8, 48.2, 76.5, 81.1, 128.3, 129.8, 134.3, 139.4,
156.6; HRMS calcd for C23H23F17NO3þ, 684.1401 (etBuþ, þHþ);
found 684.1381.
NMR (CD3OD) d 22.0, 25.2, 27.2, 33.4, 40.8, 50.2, 68.5, 77.0, 106e121
(8 fluorinated carbon), 116.5, 118.1, 124.1, 125.4, 129.3, 130.1, 131.0,
132.4, 142.6, 147.1, 166.7; HRMS calcd for C29H26F17N2O3þ, 773.1666
(þHþ); found 733.1669.
4.2.7. tert-Butyl
5-(indolin-1-yl)-5-oxopentyl(4-(2-perfluoroctyl-
ethyl)benzyloxy)carbamate (2g). Prepared by general procedure A
to give 681 mg (52%) of 2g as
a
white solid. Purity by
LCeUV(ELS)¼96%(100%); 1H NMR
d
1.50 (s, 9H), 1.69e1.81 (m, 4H),
4.3.4. N-(4-methylbenzyl)-O-(4-(2-perfluoroctylethyl)benzyl)hy-
droxylamine hydrochloride (3e). Prepared by general procedure B to
give 1.57 g (101%) of 3e as a white solid. Purity by LCeUV(ELS)¼
2.28e2.47 (m, 4H), 2.88e2.94 (m, 2H), 3.17 (t, J¼8.4 Hz, 2H), 3.48
(t, J¼6.5 Hz, 2H), 4.02 (t, J¼8.4 Hz, 2H), 4.82 (s, 2H), 6.98e7.03 (m,
1H), 7.15e7.21 (m, 4H), 7.37 (d, J¼7.8 Hz, 2H), 8.23 (d, J¼7.9 Hz,
100%(100%); 1H NMR (MeOD)
d 2.38 (s, 3H), 2.43e2.55 (m, 2H),
1H); 13C NMR
d
21.7, 26.2, 26.7, 28.0, 28.3, 32.9, 35.3, 47.9, 49.3,
2.95e3.00 (m, 2H), 4.48 (s, 2H), 5.07 (s, 2H), 7.29 (d, J¼7.8 Hz, 2H),
76.6, 81.3, 117.0, 123.5, 124.5, 127.5, 128.4, 129.9, 131.0, 134.1, 139.4,
143.0, 156.6, 170.9; HRMS calcd for C35H36F17N2O4þ, 871.2398
(þHþ); found 871.2410.
7.34e7.41 (m, 6H); 13C NMR (CD3OD)
d
21.3, 27.2, 33.4 (t, J¼22 Hz),
54.5, 77.1, 106e121 (8 fluorinated carbon), 126.9, 130.0, 130.8, 130.9,
131.8, 132.5, 141.5, 142.5; HRMS calcd for C25H21F17NOþ, 674.1346
(þHþ); found 674.1335.
4.2.8. tert-Butyl (3-(3-acetyl-1H-indol-1-yl)propyl)((4-(2-
perfluoroctylethyl)benzyl)oxy)carbamate (2h). Prepared by general
procedure A to give 1.266 g (98%) of 2h as a white solid. Purity by
4.3.5. N-Isopentyl-O-(4-(2-perfluoroctylethyl)benzyl)hydroxylamine
hydrochloride (3f). Prepared by general procedure B to give 2.66 g
(99%) of 3f as a white solid. Purity by 1H NMR >90%; 1H NMR
LCeUV(ELS)¼100%(100%); 1H NMR
d 1.50 (s, 9H), 2.13e2.19 (m,
4H), 2.29e2.41 (m, 2H), 2.49 (s, 3H), 2.89e2.93 (m, 2H), 3.47 (t,
J¼6.4 Hz, 2H), 4.18 (t, J¼7.0 Hz, 2H), 4.79 (s, 2H), 7.17e7.21 (m, 2H),
(CD3OD)
d
0.91 (d, J¼6.6 Hz, 6H), 1.69 (hept, J¼ Hz, 1H), 1.77e1.83
(m, 2H), 2.27e2.39 (m, 2H), 2.84e2.90 (m, 2H), 3.23e3.30 (m, 2H),
5.32 (s, 2H), 7.21 (d, J¼8 Hz, 2H), 7.39 (d, J¼8 Hz, 2H); HRMS calcd
for C22H23F17NOþ, 640.1503 (þHþ); found 640.1492.
7.25e7.33 (m, 5H), 7.78 (s, 1H), 8.37e8.40 (m, 2H); 13C NMR
d 27.5,
28.2, 32.8 (t, J¼22 Hz), 44.4, 46.6, 76.5, 81.9, 109.7, 117.0, 122.5,
122.7, 123.2, 126.4, 128.4, 129.8, 133.7, 135.0, 136.6, 139.7, 156.4,
192.9; HRMS calcd for C35H34F17N2O4þ, 869.2242 (þHþ); found
869.2251.
4.3.6. 1-(Indolin-1-yl)-5-(((4-(2-perfluoroctylethyl)benzyl)oxy)-
amino)pentan-1-one hydrochloride (3g). Prepared by general pro-
cedure B to give 481 mg (100%) of 3g as a white solid. Purity by
LCeUV(ELS)¼98%(100%); 1H NMR (CD3OD)
d 1.77e1.90 (m, 4H),
4.3. General procedure B (Boc-deprotection of fBnOeNRBoc)
2.41e2.54 (m, 2H), 2.61 (t, J¼6.5 Hz, 2H), 2.94e2.99 (m, 2H), 3.20 (t,
J¼8.4 Hz, 2H), 3.41 (t, J¼7.2 Hz, 2H), 4.11 (t, J¼8.4 Hz, 2H), 5.11 (s,
2H), 7.01e7.05 (m, 1H), 7.13e7.18 (m, 1H), 7.21e7.25 (m, 1H), 7.35 (d,
J¼8.0 Hz, 2H), 7.43 (d, J¼8.0 Hz, 2H), 8.11 (d, J¼8.1 Hz, 1H); 13C NMR
A mixture of absolute ethanol (15 mL) was slowly added acetyl
chloride (2.5 mL, 34 mmol) and stirred for 5 min. To it was added
Boc-protected substrate (2e3 mmol) and the mix was stirred
under argon overnight. TLC (heptane/ethyl acetate 3:1) showed
completion of the reaction in all cases except 3b in this case
stirring for 48 h was necessary. The solvent and excess HCl was
removed in vacuo to give the hydrochloride salts of the per-
fluorobenzyloxyamines. The average purity by LCeUV was 98%.
d
20.9, 23.6, 26.2, 28.1, 32.5, 32.7, 32.8, 32.4, 33.4, 35.1, 48.3, 76.4,
106e121 (8 fluorinated carbon), 117.1, 124.1, 124.7, 127.5, 128.7,
130.4, 131.2, 131.3, 140.6, 142.6, 171.1; HRMS calcd for
C30H28F17N2O2þ, 771.1874 (þHþ); found 771.1862.
4.3.7. 1-(1-(3-(((4-(2-Perfluoroctylethyl)benzyl)oxy)amino)propyl)-
1H-indol-3-yl)ethanone hydrochloride (3h). Prepared by general
procedure B to give 203 mg (100%) of 3h as a pink solid. Purity by
4.3.1. N-Methyl-O-(4-(2-perfluoroctylethyl)benzyl)hydroxylamine
hydrochloride (3a). Prepared by general procedure B to give 119 mg
(97%) of 3a as a white solid. One spot by TLC Rf(free base)¼0.24
(heptane/ethyl acetate 3:1). Purity by NMR >90%; 1H NMR (CD3OD)
LCeUV(ELS)¼98%(100%); 1H NMR (CD3OD)
d 1.26e1.35 (m, 2H),
2.26e2.38 (m, 2H), 2.43e2.50 (m, 3H), 2.84e2.89 (m, 2H), 3.24 (t,
J¼6.9 Hz, 2H), 4.34 (t, J¼6.7 Hz, 2H), 5.24 (s, 3H), 7.19 (d, J¼8.0 Hz,
2H), 7.25e7.29 (m, 1H), 7.31e7.35 (m, 3H), 7.95 (s, 1H), 8.29e8.32
d
2.28e2.39 (m, 2H), 2.86e2.91 (m, 2H), 2.98 (s, 3H), 5.26 (s, 2H),
7.24 (d, J¼8.0 Hz, 2H), 7.41 (d, J¼8.0 Hz, 2H); 13C NMR (CD3OD)
(m, 1H); 13C NMR (CD3OD)
d
24.1, 26.2, 32.5 (t, J¼22 Hz), 43.8, 46.5,