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Y. Yamano et al. / Bioorg. Med. Chem. 20 (2012) 3658–3665
J = 6.5 Hz), 4.73 (1H, br s). 13C NMR (CDCl3) d: 14.09, 22.65, 24.92,
28.36 (C Â 4), 29.12, 29.23, 29.31, 29.43, 29.57, 29.60 (C Â 2),
29.63, 31.89, 34.26, 37.40, 61.70, 79.21, 155.86, 173.96. IR
pentadecyl ester 10d (74%) and hexadecyl ester 11e (79%) were
similarly prepared from N-boc-glycine (9).
Dodecyl 2-((tert-butoxycarbonyl)amino)acetate (10a): Colorless
oil; 1H NMR (CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26 (18H, br s), 1.45
(9H, s), 1.64 (2H, quint, J = 7 Hz), 3.90 (2H, d, J = 5.5 Hz), 4.14 (2H,
t, J = 7 Hz), 5.08 (1H, br s). 13C NMR (CDCl3) d: 14.05, 22.62,
25.75, 28.23 (C Â 3), 28.47, 29.15, 29.28, 29.43, 29.50, 29.55,
m
max(CHCl3) cmÀ1: 3458, 1732 (sh), 1712. HR-SIMS m/z: 408.3082
(MNa+, C22H43O4NNa requires 408.3084).
3-((tert-Butoxycarbonyl)amino)propyl hexadecanoate (7d):
Colorless solid; 1H NMR (300 MHz, CDCl3) d: 0.88 (3H, t, J = 7 Hz),
1.25 (24H, br s), 1.44 (9H, s), 1.61 (2H, quint, J = 7.5 Hz), 1.81
(2H, quint, J = 6.5), 2.30 (2H, t, J = 7.5 Hz), 3.19 (2H, q, J = 6.5 Hz),
4.14 (2H, t, J = 6.5 Hz), 4.73 (1H, br s). 13C NMR (75 MHz, CDCl3)
d: 14.10, 22.67, 24.93, 28.37 (C Â 4), 29.15, 29.25, 29.34, 29.44,
29.58, 29.63 (C Â 2), 29.66 (C Â 3), 31.90, 34.27, 37.42, 61.71,
29.57, 31.85, 42.36, 65.43, 79.81, 155.63, 170.40. IR
cmÀ1
19H38O4N requires 344.2795).
Tridecyl 2-((tert-butoxycarbonyl)amino)acetate (10b): Color-
mmax(CHCl3)
:
3449, 1742, 1712. HR-SIMS m/z: 344.2790 (MH+,
C
less oil; 1H NMR (CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26 (20H, br s),
1.45 (9H, s), 1.64 (2H, quint, J = 7 Hz), 3.90 (2H, d, J = 5.5 Hz),
4.14 (2H, t, J = 7 Hz), 5.04 (1H, br s). 13C NMR (CDCl3) d: 14.09,
22.66, 25.79, 28.28 (C Â 3), 28.50, 29.19, 29.32, 29.46, 29.54,
29.61 (C Â 2), 29.63, 31.89 42.41, 65.49, 79.90, 155.66, 170.41. IR
79.23 155.88, 173.98. IR
m
max(CHCl3) cmÀ1: 3458, 1729 (sh),
1712. HR-SIMS m/z: 436.3393 (MNa+, C24H47O4NNa requires
436.3397).
3.1.4. Preparation of 3-aminopropyl esters 8a–d
m
max(CHCl3) cmÀ1: 3448, 1742, 1713. HR-SIMS m/z: 358.2943
In a manner similar to that for the preparation of 2-aminoethyl
esters 5a–d from N-boc-2-aminoethyl esters 4a–d, N-boc-3-ami-
nopropyl esters 7b–d were treated with TFA to provide amines
8a (quant), 8b (71%), 8c (47%) and 8d (42%).
(MH+, C20H40O4N requires 358.2952).
Tetradecyl 2-((tert-butoxycarbonyl)amino)acetate
(10c):
Colorless oil; 1H NMR (CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26 (22H,
br s), 1.45 (9H, s), 1.65 (2H, quint, J = 7 Hz), 3.90 (2H, d,
J = 5.5 Hz), 4.14 (2H, t, J = 7 Hz), 5.01 (1H, br s). 13C NMR (CDCl3)
d: 14.10, 22.67, 25.79, 28.28 (C Â 3), 28.50, 29.19, 29.33, 29.47,
29.54, 29.63 (C Â 3), 29.66, 31.90, 42.41, 65.51, 79.91, 155.65,
3-Aaminopropyl decanoate (8a): Colorless solid; 1H NMR
(CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.27 (12H, br s), 1.60 (2H, quint,
J = 7.5 Hz), 2.07 (2H, quint, J = 6.5), 2.31 (2H, t, J = 7.5 Hz), 3.07
(2H, t, J = 6.5 Hz), 4.19 (2H, t, J = 6.5 Hz), 7.68 (2H, br s). 13C NMR
(CDCl3) d: 14.08, 22.64, 24.80, 26.75, 29.12, 29.25 (C Â 2), 29.40,
170.44. IR
372.3103 (MH+, C21H42O4N requires 372.3108).
Pentadecyl 2-((tert-butoxycarbonyl)amino)acetate
m
max(CHCl3) cmÀ1: 3449, 1741, 1712. HR-SIMS m/z:
31.83, 34.06, 36.95, 60.66, 174.30. IR
m
max(CHCl3) cmÀ1: 3550-
(10d):
2450 (br), 1734, 1680. HR-SIMS m/z: 230.2115 (MH+, C13H28O2N
requires 230.2115).
Colorless solid; 1H NMR (CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26
(24H, br s), 1.45 (9H, s), 1.63 (2H, quint, J = 7 Hz), 3.90 (2H, d,
J = 5.5 Hz), 4.14 (2H, t, J = 7 Hz), 5.06 (1H, br s). 13C NMR (CDCl3)
d: 14.07, 22.64, 25.77, 28.26 (C Â 3), 28.49, 29.18, 29.31, 29.45,
29.52, 29.61 (C Â 3), 29.64 (C Â 2), 31.88, 42.39, 65.46, 79.84,
3-Aaminopropyl dodecanoate (8b): Colorless solid; 1H NMR
(CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.27 (16H, br s), 1.59 (2H, quint,
J = 7.5 Hz), 2.04 (2H, quint, J = 6.5), 2.30 (2H, t, J = 7.5 Hz), 3.05
(2H, t, J = 6.5 Hz), 4.17 (2H, t, J = 6.5 Hz), 7.98 (2H, br s). 13C NMR
(CDCl3) d: 14.09, 22.66, 24.79, 26.69, 29.12, 29.25, 29.32, 29.45,
155.64, 170.39. IR
m/z: 386.3209 (MH+, C22H44O4N requires 386.3265).
Hexadecyl 2-((tert-butoxycarbonyl)amino)acetate
m
max(CHCl3) cmÀ1: 3448, 1741, 1713. HR-SIMS
29.60 (C Â 2), 31.89, 34.01, 36.85, 60.59, 174.35. IR
m
max(CHCl3)
(10e);
cmÀ1: 3550-2450 (br), 1733, 1682. HR-SIMS m/z: 258.2426 (MH+,
Colorless solid; 1H NMR (CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26
(26H, br s), 1.45 (9H, s), 1.63 (2H, quint, J = 7 Hz), 3.90 (2H, d,
J = 5.5 Hz), 4.14 (2H, t, J = 7 Hz), 5.04 (1H, br s). 13C NMR (CDCl3)
d: 14.07, 22.65, 25.78, 28.26 (C Â 3), 28.50, 29.19, 29.32, 29.46,
29.53, 29.62 (C Â 3), 29.66 (C Â 3), 31.89, 42.40, 65.47, 79.86,
C
15H32O2N requires 258.2426).
3-Aaminopropyl tetradecanoate (8c): Colorless solid; 1H NMR
(CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26 (20H, br s), 1.60 (2H, quint,
J = 7.5 Hz), 2.16 (2H, quint, J = 6.5), 2.32 (2H, t, J = 7.5 Hz), 3.14
(2H, t, J = 6.5 Hz), 4.22 (2H, t, J = 6.5 Hz), 8.32 (2H, br s). 13C NMR
(CDCl3) d: 14.09, 22.66, 24.83, 26.76, 29.17, 29.29, 29.33, 29.48,
155.66, 170.40. IR m
max(CHCl3) cmÀ1: 3450, 1743, 1713. HR-SIMS
m/z: 400.3415 (MH+, C23H46O4N requires 400.3421).
29.63 (C Â 4), 31.89, 34.14, 37.07, 60.77, 174.03. IR
mmax(CHCl3)
cmÀ1: 3550-2450 (br), 1734, 1682. HR-SIMS m/z: 286.2741 (MH+,
3.1.6. Preparation of aminoacetates 11a–d
C
17H36O2N requires 286.2741).
In a manner similar to that for the preparation of 2-aminoethyl
esters 5a–d from N-boc-2-aminoethyl esters 4a–d, N-boc-amin-
oacetates 10a–e were treated with TFA to provide amines 11a
(46%), 11b (99%), 11c (46%), 11d (84%) and 11e (77%).
3-Aaminopropyl hexadecanoate (8d): Colorless solid; 1H NMR
(CDCl3 + CD3OD) d: 0.88 (3H, t, J = 7 Hz), 1.26 (24H, br s), 1.60
(2H, quint, J = 7.5 Hz), 2.09 (2H, quint, J = 6.5), 2.33 (2H, t,
J = 7.5 Hz), 3.04 (2H, t, J = 6.5 Hz), 4.18 (2H, t, J = 6.5 Hz). 13C NMR
(CDCl3 + CD3OD) d: 13.90, 22.51, 24.67, 26.42, 28.99, 29.11, 29.19,
29.31, 29.44, 29.48 (C Â 2), 29.51 (C Â 3), 31.75, 33.93, 36.81,
Dodecyl 2-aminoacetate (11a): Colorless solid; 1H NMR
(CDCl3 + CD3OD) d: 0.88 (3H, t, J = 7 Hz), 1.26 (18H, br s), 1.62
(2H, quint, J = 7 Hz), 3.57 (2H, br s), 4.13 (2H, t, J = 7 Hz). 13C
NMR (CDCl3 + CD3OD) d: 13.92, 22.54, 25.62, 28.30, 29.06, 29.20,
29.34, 29.42, 29.47 (C Â 2), 31.77, 41.46, 65.93, 170.77. IR
60.83, 174.13. IR
m
max(KBr) cmÀ1: 3461, 1742. HR-SIMS m/z:
314.3053 (MH+, C19H40O2N requires 314.3054).
m
max(CHCl3) cmÀ1: 3392, 1734 (sh), 1680. HR-SIMS m/z: 244.2267
3.1.5. Preparation of N-boc-aminoacetates 10a–e
(MH+, C14H30O2N requires 244.2271).
2-Chloro-1-methylpyridinium iodide (CMPI, 3.32 g, 13 mmol)
and N,N-dimethylaminopyridine (DMAP, 3.18 g, 26 mmol) were
added to a solution of N-boc-glycine (9) (1.75 g, 10 mmol) and
dodecanol (2.47 mL, 10 mmol) in dry DCM (20 mL) at 0 °C and
the mixture was stirred at 0 °C for 30 min. After the mixture was
diluted with AcOEt, the resulting precipitates were filtered off.
The filtrates were successively washed with aqueous 5% HCl,
saturated aqueous NaHCO3 and brine, dried over Na2SO4, and
evaporated. The resulting crude product was purified by flash CC
(silica gel; AcOEt/DCM, 5:95) to provide the dodecyl ester 10a
(2.78 g, 81%). Tridecyl ester 10b (86%), tetradecyl ester 10c (82%),
Tridecyl 2-aminoacetate (11b): Colorless solid; 1H NMR (CDCl3)
d: 0.88 (3H, t, J = 7 Hz), 1.26 (20H, br s), 1.47 (2H, br s), 1.64 (2H,
quint, J = 7 Hz), 3.42 (2H, s), 4.13 (2H, t, J = 7 Hz). 13C NMR (CDCl3)
d: 14.04, 22.62, 25.81, 28.56, 29.17, 29.28, 29.44, 29.50, 29.57
(C Â 2), 29.60, 31.85, 43.94, 65.01, 174.33. IR
m :
max(CHCl3) cmÀ1
3398, 1734. HR-SIMS m/z: 258.2422 (MH+, C15H32O2N requires
258.2428).
Tetradecyl 2-aminoacetate (11c): Colorless solid; 1H NMR
(CDCl3) d: 0.88 (3H, t, J = 7 Hz), 1.26 (22H, br s), 1.44 (2H, br s),
1.63 (2H, quint, J = 7 Hz), 3.42 (2H, s), 4.12 (2H, t, J = 7 Hz). 13C
NMR (CDCl3) d: 14.08, 22.65, 25.84, 28.58, 29.20, 29.32, 29.47,