PAPER
Selective Protection of Aromatic Amines in the Presence of Aliphatic Amines
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J = 8.2 Hz, 1 H), 6.93–6.96 (m, 1 H), 6.66–6.69 (m, 1 H), 4.46 (d,
J = 6.8 Hz, 2 H), 4.26 (t, J = 6.8 Hz, 1 H), 4.19 (t, J = 4.9 Hz, 2 H),
3.34 (t, J = 5.1 Hz, 2 H).
13C NMR (101 MHz, CD3OD): d = 157.17, 152.97, 142.47, 139.88,
138.79, 128.01, 126.10, 125.45, 123.39, 118.26, 110.40, 107.36,
103.71, 64.99, 62.44, 45.57, 37.56.
4¢-(Aminomethyl)-N-(9-fluorenylmethoxycarbonyl)-1,1¢-biphe-
nyl-4-ylamine Hydrochloride (Entry 13)
Conversion by HPLC: 94%; a portion of this material was isolated
and characterized: pale yellow solid; mp >240 °C (dec).
1H NMR (400 MHz, DMSO-d6): d = 9.89 (br s, 1 H), 8.59 (br s, 2
H), 7.89 (d, J = 7.4 Hz, 2 H), 7.75 (d, J = 7.2 Hz, 2 H), 7.64 (d,
J = 7.6 Hz, 2 H), 7.54–7.59 (m, 6 H), 7.41 (t, J = 7.2 Hz, 2 H), 7.33
(t, J = 7.2 Hz, 2 H), 4.48 (d, J = 6.3 Hz, 2 H), 4.30 (t, J = 6.7 Hz, 1
H), 4.01 (br s, 2 H).
13C NMR (101 MHz, DMSO-d6): d = 154.10, 144.45, 141.50,
140.40, 139.47, 134.15, 133.39, 130.27, 128.40, 127.84, 127.67,
126.89, 125.86, 120.90, 119.34, 66.31, 47.30, 42.50.
MS (ESI): m/z = 375 [M + H+].
7-(9-Fluorenylmethoxycarbonylamino)-1,2,3,4-tetrahydroiso-
quinoline Hydrochloride (Entry 9)
Pale yellow solid; yield: 78%; mp >270 °C (dec).
1H NMR (400 MHz, CD3OD): d = 7.79 (d, J = 7.6 Hz, 2 H), 7.68 (d,
J = 7.4 Hz, 2 H), 7.39 (t, J = 7.4 Hz, 3 H), 7.28–7.33 (m, 3 H), 7.13
(d, J = 8.4 Hz, 1 H), 4.47 (br s, 2 H), 4.23–4.28 (m, 3 H), 3.46 (td,
J = 3.3, 6.5 Hz, 2 H), 3.04 (t, J = 6.3 Hz, 2 H).
13C NMR (101 MHz, CD3OD): d = 154.54, 144.04, 141.47, 138.07,
129.39, 128.39, 127.67, 127.02, 125.73, 124.93, 119.83, 118.73,
116.32, 66.51, 44.71, 41.84, 24.29.
LRMS (ESI): m/z = 404 [M + H+– NH3].
N-(2-Aminoethyl)-4-(9-fluorenylmethoxycarbonylamino)benz-
amide Hydrochloride (Entry 14)
White solid; yield: 87%; mp 231–233 °C.
1H NMR (400 MHz, DMSO-d6): d = 10.01 (br s, 1 H), 8.68 (t,
J = 5.6 Hz, 1 H), 8.11 (br s, 2 H), 7.98 (d, J = 7.2 Hz, 2 H), 7.85 (d,
J = 8.8 Hz, 2 H), 7.74 (d, J = 7.6 Hz, 2 H), 7.51 (br s, 2 H), 7.31–
7.43 (m, 5 H), 4.49 (d, J = 6.8 Hz, 2 H), 4.30 (t, J = 6.4 Hz, 1 H),
3.47–3.51 (m, 2 H), 2.93–2.97 (m, 2 H).
13C NMR (101 MHz, DMSO-d6): d = 166.90, 153.99, 144.39,
142.62, 141.50, 129.05, 128.41, 127.84, 125.82, 120.91, 117.91,
66.43, 47.24, 39.33, 37.74.
MS (ESI): m/z = 371 [M + H+].
5-(9-Fluorenylmethoxycarbonylamino)indan-2-amine Hydro-
chloride (Entry 10)
White solid; yield: 81%; mp 208–210 °C.
1H NMR (400 MHz, CD3OD): d = 7.81 (d, J = 7.4 Hz, 2 H), 7.69 (d,
J = 7.4 Hz, 2 H), 7.42–7.52 (m, 1 H), 7.40 (t, J = 7.4 Hz, 2 H), 7.28–
7.34 (m, 2 H), 7.15–7.23 (m, 2 H), 4.48–4.52 (m, 2 H), 4.27 (t,
J = 6.5 Hz, 1 H), 4.04–4.10 (m, 1 H), 3.34–3.39 (m, 2 H), 2.92–3.01
(m, 2 H).
13C NMR (101 MHz, CD3OD): d = 153.15, 142.49, 139.87, 138.33,
136.90, 132.07, 126.11, 125.46, 123.41, 123.33, 118.28, 116.82,
113.78, 64.95, 50.12, 45.58, 36.13, 35.41.
MS (ESI): m/z = 402 [M + H+].
4-(2-Aminoethyl)-N-(benzyloxycarbonyl)phenylamine (1c);
Typical Procedure
To a soln of 4-aminophenethylamine (0.32 g, 2.33 mmol) in 10% aq
AcOH (20 mL) was added CbzCl (0.42 g, 2.44 mmol) dissolved in
1,4-dioxane (20 mL). The mixture was stirred overnight at r.t. H2O
(100 mL) was added and the mixture was washed with Et2O (3 × 50
mL). The aqueous phase was made basic with 2 N NaOH to pH 14
and extracted with Et2O (3 × 75 mL). The combined extract was
washed with H2O (2 × 40 mL), dried (Na2SO4), filtered and concen-
trated under reduced pressure to give the expected product 1c.
MS (ESI): m/z = 371 [M + H+].
Methyl (S)-2-Amino-3-[4-(9-fluorenylmethoxycarbonylami-
no)phenyl]propionate Hydrochloride (Entry 11)
White solid; yield: 80%; mp 203–205 °C.
1H NMR (400 MHz, CD3OD): d = 7.79 (d, J = 7.4 Hz, 2 H), 7.68 (d,
J = 7.4 Hz, 2 H), 7.37–7.46 (m, 4 H), 7.29–7.33 (m, 2 H), 7.15 (d,
J = 8.4 Hz, 2 H), 4.48 (d, J = 6.5 Hz, 2 H), 4.24–4.29 (m, 2 H), 3.80
(s, 3 H), 3.21 (dd, J = 6.1, 14.5 Hz, 1 H), 3.11 (dd, J = 7.4, 14.5 Hz,
1 H).
13C NMR (101 MHz, CD3OD): d = 169.30, 154.63, 144.06, 141.47,
138.82, 129.72, 128.36, 127.67, 127.02, 125.00, 119.87, 119.76,
119.31, 66.53, 54.02, 52.50, 35.56.
Pale yellow solid; yield: 93% (98% conversion by HPLC); mp 151–
153 °C.
1H NMR (400 MHz, CD3OD): d = 7.30–7.42 (m, 7 H), 7.13 (d,
J = 8.6 Hz, 2 H), 5.16 (s, 2 H), 2.87 (t, J = 6.8 Hz, 2 H), 2.72 (t,
J = 7.0 Hz, 2 H).
13C NMR (101 MHz, DMSO-d6): d = 166.71, 154.08, 137.38,
135.37, 129.66, 129.12, 128.75, 118.85, 66.30, 53.28, 36.77, 29.42.
MS (ESI): m/z = 271 [M + H+].
MS (ESI): m/z = 417 [M + H+].
Protection with Cbz (Table 1, Last Yield Column)
3-(2-Aminoethyl)-N-(benzyloxycarbonyl)phenylamine (Entry
2)
(S)-2-Amino-3-[4-(9-fluorenylmethoxycarbonylamino)phe-
nyl]propionic Acid Hydrochloride (Entry 12)
White solid; yield: 86%; mp 216–218 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.69 (br s, 1 H), 7.88 (d, J = 7.4
Hz, 2 H), 7.72 (d, J = 7.4 Hz, 2 H), 7.27–7.42 (m, 6 H), 7.15 (d,
J = 8.4 Hz, 2 H), 4.44 (d, J = 6.8 Hz, 2 H), 4.26–4.29 (m, 1 H),
3.54–3.59 (m, 1 H), 3.07 (dd, J = 4.9, 14.3 Hz, 1 H), 2.89 (dd,
J = 7.4, 14.3 Hz, 1 H).
White solid; yield: 81%; mp 79–81 °C.
1H NMR (400 MHz, CDCl3): d = 7.33–7.40 (m, 5 H), 7.21–7.26 (m,
3 H), 6.87–6.90 (m, 1 H), 5.18 (s, 2 H), 2.94 (br s, 2 H), 2.70 (t,
J = 6.8 Hz, 2 H).
13C NMR (101 MHz, CDCl3): d = 153.70, 141.11, 138.34, 136.37,
129.34, 128.85, 128.57, 128.52, 124.17, 119.30, 116.81, 67.15,
43.56, 40.21.
13C NMR (101 MHz, DMSO-d6): d = 170.87, 154.11, 144.45,
141.47, 138.36, 131.26, 130.46, 128.38, 127.81, 125.88, 120.93,
119.02, 66.17, 55.44, 47.30, 36.45.
MS (ESI): m/z = 271 [M + H+].
MS (ESI): m/z = 403 [M + H+].
4-(Aminomethyl)-N-(benzyloxycarbonyl)phenylamine (Entry
3)
White solid; yield: 97%.
Synthesis 2009, No. 2, 283–289 © Thieme Stuttgart · New York