1944
R. Csütörtöki et al.
LETTER
height width (corresponding to ca. 15 nm at 225 nm), using dipole-
velocity-computed rotational strengths. The MOLEKEL26 software
package was used for visualization of the results.
Benzyl carbamate was prepared according to a literature process.27
Ethyl 2-(Benzyloxycarbonylamino)-2-(1¢-hydroxynaphthalen-
2¢-yl)acetate (6b)
Prepared similarly to 6a. The reaction mixture was stirred at reflux
temperature for 97 h. The solvent was removed under reduced pres-
sure, and the product was isolated by column chromatography; elu-
ent: n-hexane–EtOAc (2:1).
Yellowish oil, yield 27%. 1H NMR (400 MHz, DMSO-d6): d = 1.11
(3 H, t, J = 7.0 Hz), 4.14 (2 H, q, J = 7.1 Hz), 5.08 (2 H, s), 5.84 (1
H, d, J = 7.8 Hz), 6.83 (1 H, d, J = 7.9 Hz), 7.22 (1 H, d, J = 8.0 Hz),
7.29–7.37 (5 H, m), 7.49 (1 H, t, J = 7.2 Hz), 7.56 (1 H, t, J = 7.7
Hz), 7.94 (1 H, d, J = 8.5 Hz), 8.16 (1 H, d, J = 7.6 Hz), 8.21 (1 H,
d, J = 8.4 Hz), 10.30 (1 H, br s). 13C NMR (100 MHz, DMSO-d6):
d = 13.9, 54.5, 60.8, 65.5, 107.2, 122.4, 122.7, 122.8, 124.5, 124.8,
126.3, 126.4, 126.8, 127.6, 127.7, 128.3, 128.4, 132.0, 136.9, 153.7,
155.9, 171.4. Anal. Calcd for C22H21NO5 (379.41): C, 69.64; H,
5.58; N, 3.69. Found: C, 69.61; H, 5.53; N, 3.61.
Methyl 2-(Benzyloxycarbonylamino)-2-(2¢-hydroxynaphtha-
len-1¢-yl)acetate (2a)
A mixture of 2-naphthol (0.72 g, 5.0 mmol), glyoxylic acid mono-
hydrate (0.50 g, 5.5 mmol), benzyl carbamate (0.90 g, 6.0 mmol),
and PTSA·H2O (0.95 g, 5.0 mmol) was dissolved in MeOH (15
mL), and the solution was refluxed in an oil bath. After 2 h, the re-
action product started to separate out as white crystals from the re-
action mixture, which was refluxed for a further 24 h. The mixture
was cooled down to 5–10 °C. The separated crystals were filtered
off, washed with cold MeOH (2 × 5 mL), and recrystallized from
MeOH (20 mL).
White crystals, yield 1.26 g (69%), mp 195–197 °C. 1H NMR (400
MHz, DMSO-d6): d = 3.59 (3 H, s), 5.09 (2 H, m), 6.11 (1 H, d,
J = 8.4 Hz), 7.18 (1 H, d, J = 8.9 Hz), 7.28–7.39 (6 H, m), 7.48 (1
H, t, J = 7.5 Hz), 7.65 (1 H, d, J = 8.2 Hz), 7.76–7.90 (3 H, m),
10.16 (1 H, br s). 13C NMR (100 MHz, DMSO-d6): d = 50.7, 53.0,
66.5, 115.6, 119.0, 123.0, 123.5, 127.7, 128.5, 128.6, 129.0, 129.2,
129.4, 130.8, 133.4, 137.8, 154.1, 157.1, 173.0. Anal. Calcd for
C21H19NO5 (365.38): C, 69.03; H, 5.24; N, 3.83. Found: C, 68.89;
H, 5.13; N, 3.75.
General Method for Removal of the Benzyloxycarbonyl Group
Compound 2a or 6a, and 2b or 6b (2.0 mmol) was dissolved in
MeOH (15 mL). In parallel, Pd/C (0.44 g) was suspended in MeOH
or EtOH in case of 2b and 6b (10 mL). The mixture was hydroge-
nated at atmospheric pressure for 1 h. The catalyst was then filtered
off and washed with MeOH (2 × 10 mL). The filtrate was concen-
trated to dryness under reduced pressure and dissolved in EtOH (5
mL). HCl–EtOH (22%; 0.35 mL, 2.0 mmol) and Et2O (20 mL) were
added to crystallize 3a,b and 7a,b.
Ethyl 2-(Benzyloxycarbonylamino)-2-(2¢-hydroxynaphthalen-
1¢-yl)acetate (2b)
Prepared similarly to 2a in EtOH. After a reaction time of 94 h, the
solvent was evaporated off and the product was isolated by column
chromatography (n-hexane/EtOAc, 2:1), followed by crystalliza-
tion from iPr2O (15 mL).
Methyl 2-Amino-2-(2¢-hydroxynaphthalen-1¢-yl)acetate Hydro-
chloride (3a)
Green crystals, yield 0.40 g (75%), mp 187–189 °C. 1H NMR (400
MHz, DMSO-d6): d = 3.68 (3 H, s), 5.93 (1 H, s), 7.38 (2 H, d,
J = 7.5 Hz), 7.56 (1 H, t, J = 7.7 Hz), 7.90 (2 H, t, J = 8.3 Hz), 8.04
(1 H, d, J = 8.6 Hz), 8.85 (3 H, br s). 13C NMR (100 MHz, DMSO-
d6): d = 49.1, 53.8, 111.6, 118.6, 122.7, 123.9, 128.1, 128.8, 129.5,
132.3, 133.4, 155.3, 170.6. Anal. Calcd for C13H14ClNO3 (267.71):
C, 58.32; H, 5.27; N, 5.23. Found: C, 58.28; H, 5.18; N, 5.21.
1
White crystals, yield 34%, mp 147–149 °C. H NMR (400 MHz,
DMSO-d6): d = 1.06 (3 H, t, J = 6.9 Hz), 4.07 (2 H, q, J = 7.0 Hz),
5.08 (2 H, m), 6.06 (1 H, d, J = 8.3 Hz), 7.17 (1 H, d, J = 8.8. Hz),
7.27–7.37 (6 H, m), 7.47 (1 H, t, J = 7.5 Hz), 7.64 (1 H, d, J = 8.2
Hz), 7.74–7.88 (3 H, m), 10.12 (1 H, br s). 13C NMR (100 MHz,
DMSO-d6): d = 13.9, 49.9, 60.6, 65.5, 114.7, 118.0, 122.1, 122.5,
126.8, 127.5, 127.7, 128.0, 128.2, 128.4, 129.8, 132.5, 136.9, 153.2,
156.1, 171.4. Anal. Calcd for C22H21NO5 (379.41): C, 69.64; H,
5.58; N, 3.69. Found: C, 69.59; H, 5.49; N, 3.58.
Ethyl 2-Amino-2-(2¢-hydroxynaphthalen-1¢-yl)acetate Hydro-
chloride (3b)
Beige crystals, yield 0.40 g (72%), mp 132–135 °C. 1H NMR (400
MHz, DMSO-d6): d = 1.10 (3 H, t, J = 7.1 Hz), 4.17 (2 H, q, J = 7.0
Hz), 5.91 (1 H, s), 7.27 (1 H, d, J = 8.9 Hz), 7.38 (1 H, t, J = 7.5 Hz),
7.56 (1 H, t, J = 7.6 Hz), 7.86–7.94 (2 H, m), 8.05 (1 H, d, J = 8.3
Hz), 8.56 (3 H, br s), 10.84 (1 H, br s). 13C NMR (100 MHz, DMSO-
d6): d = 13.8, 48.3, 61.7, 110.8, 117.6, 121.8, 122.9, 127.2, 127.9,
128.6, 131.4, 132.5, 154.3, 169.2. Anal. Calcd for C14H16ClNO3
(281.73): C, 59.68; H, 5.72; N, 4.97. Found: C, 59.64; H, 5,63; N,
4.92.
Methyl 2-(Benzyloxycarbonylamino)-2-(1¢-hydroxynaphtha-
len-2¢-yl)acetate (6a)
To a mixture of 1-naphthol (0.72 g, 5.0 mmol), glyoxylic acid
monohydrate (0.50 g, 5.5 mmol), and benzyl carbamate (0.90 g, 6.0
mmol) in MeOH (15 mL) PTSA·H2O (0.95 g, 5.0 mmol) was added,
and the reaction mixture was then stirred at reflux temperature. Af-
ter 5 h, the reaction product started to separate out as white crystals
from the reaction mixture, which was refluxed for a further 31 h.
The mixture was cooled down to 5–10 °C. The separated crystals
were filtered off, washed with cold MeOH (2 × 5 mL), and recrys-
tallized from MeOH (22 mL).
White crystals, yield 0.97 g (53%), mp 180–182 °C. 1H NMR (400
MHz, DMSO-d6): d = 3.67 (3 H, s) 5.10 (2 H, s), 5.89 (1 H, d,
J = 7.8 Hz), 6.85 (1 H, d, J = 7.8 Hz), 7.24 (1 H, d, J = 7.9 Hz),
7.29–7.41 (5 H, m), 7.50 (1 H, t, J = 7.6 Hz), 7.59 (1 H, t, J = 7.5
Hz), 7.96 (1 H, d, J = 8.6 Hz), 8.22 (2 H, d, J = 8.2 Hz), 10.31 (1 H,
br s). 13C NMR (100 MHz, DMSO-d6): d = 53.0, 55.4, 66.5, 108.1,
123.3, 123.6, 123.8, 125.5, 125.7, 127.4, 127.8, 128.5, 128.7, 129.2,
132.8, 137.8, 154.6, 156.8, 172.8. Anal. Calcd for C21H19NO5
(365.38): C, 69.03; H, 5.24; N, 3.83. Found: C, 69.09; H, 5.21; N,
3.85.
Methyl 2-Amino-2-(1¢-hydroxynaphthalen-2¢-yl)acetate Hydro-
chloride (7a)
1
Beige crystals, yield 0.45 g (84%), mp > 350 °C. H NMR (400
MHz, DMSO-d6): d = 3.71 (3 H, s), 5.94 (1 H, s), 6.97 (1 H, d,
J = 8.0 Hz), 7.47 (1 H, d, J = 8.0 Hz), 7.56 (1 H, t, J = 7.5 Hz), 7.66
(1 H, t, J = 7.5 Hz), 8.16 (1 H, d, J = 8.6 Hz), 8.26 (1 H, d, J = 8.3
Hz), 8.94 (3 H, br s), 10.72 (1 H, br s). 13C NMR (100 MHz, DMSO-
d6): d = 52.2, 53.9, 108.4, 119.7, 123.6, 123.9, 125.7, 125.9, 128.2,
132.7, 155.8, 170.5. Anal. Calcd for C13H14ClNO3 (267.71): C,
58.32; H, 5.27; N, 5.23. Found: C, 58.25; H, 5.13; N, 5.18.
Ethyl 2-Amino-2-(1¢-hydroxynaphthalen-2¢-yl)acetate Hydro-
chloride (7b)
Beige crystals, yield 0.39 g (69%), mp 197–199 °C. 1H NMR (400
MHz, DMSO-d6): d = 1.09 (3 H, t, J = 7.1 Hz), 4.18 (2 H, q, J = 6.9
Hz), 5.89 (1 H, s), 6.95 (1 H, d, J = 8.0 Hz), 7.44 (1 H, d, J = 8.1
Synlett 2011, No. 13, 1940–1946 © Thieme Stuttgart · New York