Deprotection of N-Nosyl-α-amino Acids
(8b) (0.076 g, 0.23 mmol) in dry DCM (20 mL). The reaction mix-
ture was shaken at room temperature for 1 h, and the removal of
the nosyl group was monitored by TLC (diethyl ether/petroleum
ether, 60:40). Then the resin was drained and washed with DCM
(0.23 mmol) in dry DCM (10 mL) and the mixture stirred at room
temperature for 4 h. The reaction mixture was then acidified with
1 hydrochloride acid and extracted with DCM (3ϫ10 mL). The
organic layer was washed with a saturated solution of NaHCO3
(5ϫ1 min), 2-propanol (5ϫ1 min) and DCM (5ϫ1 min). The and dried (Na2SO4). The solvent was evaporated under reduced
combined filtrates were concentrated to dryness under reduced
pressure.
pressure to afford the corresponding N-acetylphenylalanine methyl
ester (10d) as a white solid in quantitative yield. M.p. 85–88 °C. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.07–7.33 (m, 5 H, Ar-H),
6.01 (d, J = 7.12 Hz, 1 H, NH), 4.09 (m, 1 H, 2-H), 3.73 (s, 3 H,
OCH3), 3.18 (dd, J = 5.82, J = 13.82 Hz, 1 H, 3-H2), 3.07 (dd, J
= 5.97, J = 13.82 Hz, 1 H, 3-H2), 1.99 (s, 3 H, CH3CO) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 172.14, 169.67, 135.81, 129.26,
128.61, 127.17, 53.11, 52.39, 37.82, 23.18 ppm. GC-MS (EI): m/z
(%) = 221 (0.5) [M]+·, 162 (100), 131 (29), 120 (45), 91 (48), 88 (86),
43 (76). C12H15NO3 (221.25): calcd. C 65.14, H 6.83, N 6.33; found
C 65.22, H 6.86, N 6.31.
Synthesis of N-Acetylleucine Methyl Ester (10b): Acetic anhydride
(0.1 mL, 1.15 mmol) was added to a solution of 8b (0.23 mmol) in
dry DCM (10 mL) and the mixture stirred at room temperature for
4 h. The reaction mixture was then acidified with 1 hydrochloride
acid and extracted with DCM (3ϫ10 mL). The organic layer was
washed with a saturated solution of NaHCO3 and dried (Na2SO4).
The solvent was evaporated under reduced pressure to afford the
corresponding N-acetylleucine methyl ester (10b) as a colourless oil
in quantitative yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 6.20
(d, J = 8.1 Hz,1 H, NH), 4.60 (m, 1 H, 2-H), 3.69 (s, 3 H, OCH3),
2.02 (s, 3 H, CH3CO), 1.69–1.44 (m, 3 H, 2-H2, 3-H), 0.92–0.89
[m, 6 H, (CH3)2CH] ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ =
173.84, 170.05, 52.27, 50.69, 41.54, 24.82, 23.05, 22.80, 21.91 ppm.
GC-MS (EI): m/z (%) = 187 (2) [M]+·, 144 (4), 128 (76), 99 (16),
86 (100), 43 (46). C9H17NO3 (187.24): calcd. C 57.73, H 9.15, N
7.48; found C 57.84, H 9.18, N 7.46.
Deprotection of N-Nosylalanine Methyl Ester (8e): Resin-bound
mercaptoacetic acid 5 (0.3 g, 0.33 mmol) and DBU (0.98 mL,
0.66 mmol) were added to a solution of N-nosylalanine methyl es-
ter (8e; 0.066 g, 0.23 mmol) in dry DCM (20 mL). The reaction
mixture was shaken at room temperature for 1 h, and the removal
of the nosyl group was monitored by TLC (diethyl ether/petroleum
ether, 60:40). Then the resin was drained and washed with DCM
(5ϫ1 min), 2-propanol (5ϫ1 min) and DCM (5ϫ1 min). The
combined filtrates were concentrated to dryness under reduced
pressure.
Deprotection of N-Nosylvaline Methyl Ester (8c): Resin-bound mer-
captoacetic acid
5 (0.3 g, 0.33 mmol) and DBU (0.98 mL,
0.66 mmol) were added to a solution of N-nosylvaline methyl ester
(8c; 0.073 g, 0.23 mmol) in dry DCM (20 mL). The reaction mix-
ture was shaken at room temperature for 1 h, and the removal of
the nosyl group was monitored by TLC (diethyl ether/petroleum
ether, 60:40). Then the resin was drained and washed with DCM
(5ϫ1 min), 2-propanol (5ϫ1 min) and DCM (5ϫ1 min). The
combined filtrates were concentrated to dryness under reduced
pressure.
Synthesis of N-Acetylalanine Methyl Ester (10e): Acetic anhydride
(0.1 mL, 1.15 mmol) was added to a solution of 9e (0.23 mmol) in
dry DCM (10 mL) and the mixture stirred at room temperature for
4 h. The reaction mixture was then acidified with 1 hydrochloride
acid and extracted with DCM (3ϫ10 mL). The organic layer was
washed with a saturated solution of NaHCO3 and dried (Na2SO4).
The solvent was evaporated under reduced pressure to afford the
corresponding N-acetylalanine methyl ester (10e) as a colourless oil
in quantitative yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 6.15
(br. s, 1 H, NH), 4.60 (m, 1 H, 2-H), 3.75 (s, 3 H, OCH3), 2.03 (s,
3 H, CH3CO), 1.40 (d, J = 7.2 Hz, 3 H, 3-H3) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 173.71, 171.62, 52.54, 48.02, 23.21,
18.60 ppm. GC-MS (EI): m/z (%) = 145 (5) [M]+·, 102 (3), 86 (72),
59 (3), 44 (100). C6H11NO3 (145.16): calcd. C 49.65, H 7.64, N
9.65; found C 49.73, H 7.67, N 9.63.
Synthesis of N-Acetylvaline Methyl Ester (10c): Acetic anhydride
(0.1 mL, 1.15 mmol) was added to a solution of 9c (0.23 mmol) in
dry DCM (10 mL) and the mixture stirred at room temperature for
4 h. The reaction mixture was then acidified with 1 hydrochloride
acid and extracted with DCM (3ϫ10 mL). The organic layer was
washed with a saturated solution of NaHCO3 and dried (Na2SO4).
The solvent was evaporated under reduced pressure to afford the
corresponding N-acetylvaline methyl ester (10c) as a colourless oil
in quantitative yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 6.05
(br. s, 1 H, NH), 4.57 (dd, J = 4.8, J = 8.7 Hz, 1 H, 2-H), 3.74 (s,
3 H, OCH3), 2.22–2.06 (m, 1 H, 3-H), 2.04 (s, 3 H, CH3CO), 0.93
[d, J = 6.9 Hz, 3 H, CH(CH3)2], 0.90 [d, J = 6.9 Hz, 3 H, CH-
(CH3)2] ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 173.21,
170.52, 57.02, 52.13, 31.22, 23.24, 18.87, 17.84 ppm. GC-MS (EI):
m/z (%) = 173 (0.20) [M]+·, 142 (0.45), 131 (4.5), 114 (77), 99 (23),
88 (55), 72 (100). C8H15NO3 (173.21): calcd. C 55.47, H 8.73, N
8.09; found C 55.57, H 8.76, N 8.07.
Deprotection of N-Nosylisoleucine Methyl Ester (8f): Resin-bound
mercaptoacetic acid 5 (0.3 g, 0.33 mmol) and DBU (0.98 mL,
0.66 mmol) were added to a solution of N-nosylisoleucine methyl
ester (8f; 0.076 g, 0.23 mmol) in dry DCM (20 mL). The reaction
mixture was shaken at room temperature for 1 h, and the removal
of the nosyl group was monitored by TLC (diethyl ether/petroleum
ether, 60:40). Then the resin was drained and washed with DCM
(5ϫ1 min), 2-propanol (5ϫ1 min) and DCM (5ϫ1 min). The
combined filtrates were concentrated to dryness under reduced
pressure.
Deprotection of N-Nosylphenylalanine Methyl Ester (8d): Resin-
bound mercaptoacetic acid
5 (0.3 g, 0.33 mmol) and DBU
Synthesis of N-Acetylisoleucine Methyl Ester (10f): Acetic anhy-
(0.98 mL, 0.66 mmol) were added to a solution of N-nosylphenyl-
alanine methyl ester (8d; 0.084 g, 0.23 mmol) in dry DCM (20 mL).
The reaction mixture was shaken at room temperature for 1 h, and
the removal of the nosyl group was monitored by TLC (diethyl
ether/petroleum ether, 60:40). Then the resin was drained and
washed with DCM (5ϫ1 min), 2-propanol (5ϫ1 min) and DCM
(5ϫ1 min). The combined filtrates were concentrated to dryness
under reduced pressure.
dride (0.1 mL, 1.15 mmol) was added to
a solution of 9f
(0.23 mmol) in dry DCM (10 mL) and the mixture stirred at room
temperature for 4 h. The reaction mixture was then acidified with
1 hydrochloride acid and extracted with DCM (3ϫ10 mL). The
organic layer was washed with a saturated solution of NaHCO3
and dried (Na2SO4). The solvent was evaporated under reduced
pressure to afford the corresponding N-acetylisoleucine methyl es-
ter (10f) as a colourless oil in quantitative yield. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 6.4 (d, J = 9.14 Hz, 1 H, NH), 4.66
(dd, J = 4.25, J = 9.14 Hz, 1 H, 2-H), 3.68 (s, 3 H, OCH3), 1.99 (s,
Synthesis of N-Acetylphenylalanine Methyl Ester (10d): Acetic an-
hydride (0.1 mL, 1.15 mmol) was added to a solution of 9d
Eur. J. Org. Chem. 2009, 3795–3800
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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