The Journal of Organic Chemistry
Page 6 of 10
3
26.2074, found: 326.2080; m/z calcd for C16H N O Na [M + 4.19 – 4.11 (m, 1H), 3.19 – 3.14 (m, 3H), 1.35 (s, 9H), 1.17 (d,
27 3 4
+
13
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Na] : 348.1894, found: 348.1902.
3
J = 6.6 Hz, 6H); C{ H} NMR (100 MHz, CDCl ) δ 163.3,
159.7, 155.0, 141.0, 136.5, 135.7, 129.4, 128.8, 127.3, 80.5,
Synthesis of methyl (tert-butoxycarbonyl)glycyl-L-serinate
17). The reaction was performed as described in the
procedure for compound 12 to furnish 17 in 30% yield (356
50.3, 41.3, 40.1, 28.4, 22.9. ESI HRMS m/z calcd for
+
(
C H N O Na [M + Na] : 396.1894, found: 396.1884.
20 27
3
4
1
mg): H NMR (400 MHz, CDCl
3
) δ 7.01 (d, J = 7.5 Hz, 1H),
.24 (s, 1H), 4.67 (m, 1H), 3.97 (m, 2H), 3.84 (d, J = 5.8 Hz,
H), 3.79 (s, 3H), 2.85 (t, J = 6.3 Hz, 1H), 1.46 (s, 9H);
Synthesis of (2S,3R)-3-hydroxy-1-methoxy-1-oxobutan-2-
aminium chloride (14). The reaction was performed as
.
5
2
described in the procedure for compound 11 to furnish 14 as a
13
1
1
C{ H} NMR (100 MHz, CDCl
3
) δ 170.8, 169.84, 156.4,
yellow thick oil (1463 mg, 100% yield). H NMR (400 MHz,
8
0.9, 63.1, 54.9, 52.9, 44.6, 28.4. Characterization data were
2
D O) δ 4.48-4.42 (m, 1H), 4.13 (d, 1H, J = 4 Hz), 3.88 (s, 3H),
5
3
13
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
consistent with previous literature.
1.36 (d, 3H, J = 4 Hz); C{ H} NMR (100 MHz, D
2
O) δ
169.9, 65.9, 59.0, 54.4, 19.4. Characterization data were
consistent with previous literature.
5
4
Synthesis
of
methyl
2-(((tert-butoxycarbonyl)amino)
methyl)oxazole-4-carboxylate (18). The reaction was
performed as described in the procedure for compound 13 to
furnish 18 in 55% yield (181 mg): H NMR (400 MHz,
CDCl
2
CDCl
2
literature.
Synthesis of methyl (tert-butoxycarbonyl)-L-valyl-L-
allothreoninate (15). The reaction was performed as described
1
3
) δ 8.19 (s, 1H), 5.18 (s, 1H, b), 4.50 (d, J = 5.9 Hz,
H), 3.92 (s, 3H), 1.45 (s, 9H); C{ H} NMR (100 MHz,
in the procedure for compound 12 in the main text to furnish
1
3
1
1
15 in 96% yield (1265 mg): H NMR (400 MHz, CDCl
3
) δ
3
) δ 162.4, 161.6, 155.6, 144.4, 133.5, 80.6, 52.4, 38.1,
6.78 (d, 1H, J = 8 Hz), 4.62 (dd, 1H, J
1
= 4 Hz, J
1
= 8 Hz),
8.4. Characterization data were consistent with previous
4.37-4.35 (m, 1H), 3.96-3.92 (m, 1H), 3.77 (s, 3H), 2.91 (s,
1H), 2.13-2.08 (m, 1H), 1.43 (s, 9H), 1.20 (d, 3H, J = 4 Hz),
0.99 (d, 3H, J = 8 Hz), 0.96 (d, 3H, J = 8 Hz); C{ H} NMR
53
1
3
1
Synthesis of tert-butyl ((4-(isopropylcarbamoyl)oxazol-2-
yl)methyl)carbamate (1b). The reaction was performed as
described in the procedure for compound 1a to furnish 1b in
(100 MHz, CDCl ) δ 172.4, 171.4, 156.2, 80.2, 68.3, 57.4,
3
52.7, 30.9, 28.4, 20.1, 19.3, 18.2. Characterization data were
5
5
consistent with previous literature.
1
00% yield (200 mg). Crude 1b was then purified by prep-
1
HPLC (70:30 CH
.11 (s, 1H), 6.69 (d, J = 8.0 Hz, 1H), 5.12 (s, 1H, b), 4.43 (d,
J = 5.9 Hz, 2H), 4.23 (m, 1H), 1.46 (s, 9H), 1.24 (d, J = 6.6
3
CN:H
2
O). H NMR (400 MHz, CDCl
3
) δ
Synthesis of methyl (S)-2-(1-((tert-butoxycarbonyl)amino)-2-
methylpropyl)-5 methyloxazole-4-carboxylate (16). The
reaction was performed as described in the procedure for
8
13
1
1
Hz, 6H); C{ H} NMR (100 MHz, CDCl
1
m/z calcd for C13H N O Na [M + Na] : 306.1424, found:
21 3 4
306.1420.
3
) δ 161.1, 159.6,
compound 13 to furnish 16 in 44% yield (291 mg): H NMR
55.58, 141.3, 136.7, 80.7, 41.2, 38.2, 28.5, 22.9. ESI HRMS
(400 MHz, CDCl
Hz, 1H), 3.93 (s, 3H), 2.63 (s, 3H), 2.21-2.16 (m, 1H), 1.46 (s,
9H), 0.95 (m, 6H); C{ H} NMR (100 MHz, CDCl ) δ 162.9,
3
3
) δ 5.27 (d, J = 9.5 Hz, 1H), 4.75 (t, J = 7.9
+
1
3
1
162.3, 156.4, 156.0, 127.4, 80.1, 54.3, 52.1, 33.1, 28.5, 19.0,
18.1, 12.2. Characterization data were consistent with previous
Synthesis of methyl (tert-butoxycarbonyl)-L-phenylalanyl-L-
serinate (19). The reaction was performed as described in the
procedure for compound 12 to furnish 19 in 42% yield (487
mg): H NMR (400 MHz, CDCl
5
5
literature.
1
3
) δ 7.36 – 7.14 (m, 5H), 6.79
Synthesis of tert-butyl (S)-(1-(4-(isopropylcarbamoyl)-5-
methyloxazol-2-yl)-2 methylpropyl)carbamate (2). The
reaction was performed as described in the procedure for
compound 1a. The crude product was obtained in 100% yield
(d, J = 7.3 Hz, 1H), 5.02 (d, J = 7.3 Hz, 1H), 4.60-4.57 (m,
1
3
H), 4.32 (q, J = 7.0 Hz, 1H), 4.00 – 3.82 (m, 2H), 3.75 (s,
13
1
H), 3.14-3.04 (m, 2H), 1.40 (s, 9H); C{ H} NMR (100
) δ 171.7, 170.5, 155.8, 136.5, 129.4, 128.9,
127.2, 80.8, 62.9, 56.3, 55.1, 52.9, 38.0, 28.4. Characterization
MHz, CDCl
3
(65 mg) and then purified by prep-HPLC (70:30 CH
3
CN:H
) δ 6.73 (d, J = 8.2
Hz, 1H), 5.06 (d, J = 9.3 Hz, 1H), 4.67 (m, 1H), 4.26-4.16 (m,
H), 2.61 (s, 3H), 2.15 (m, 1H), 1.46 (s, 9H), 1.24 (d, J = 6.4
2
O)
1
to furnish 2: H NMR (400 MHz, CDCl
3
5
3
data were consistent with previous literature.
1
1
3
1
Synthesis of methyl (S)-2-(1-((tert-butoxycarbonyl)amino)-2-
phenylethyl)oxazole-4-carboxylate (20). The reaction was
performed as described in the procedure for compound 13 to
furnish 20 in 57% yield (262 mg): H NMR (400 MHz,
CDCl
Hz, 6H), 0.93 (t, J = 6.8 Hz, 6H); C{ H} NMR (100 MHz,
CDCl ) δ 161.3, 160.7, 155.5, 152.8, 129.2, 80.2, 54.4, 41.0,
3
32.8, 28.5, 23.0, 18.9, 18.1, 11.8. ESI HRMS m/z calcd for
1
+
C H N O -H [M + H] : 340.2231, found: 340.2238; m/z
1
7
29
3
4
+
3
) δ 8.12 (s, 1H), 7.25-7.19 (m, 3H), 7.03 (d, J = 7.0 Hz,
17 29 3 4
calcd for C H N O Na [M + Na] : 362.2050, found:
2
9
H), 5.21 (s, 2H, b), 3.91 (s, 3H), 3.25 – 3.21 (m, 2H), 1.40 (s,
H); C{ H} NMR (100 MHz, CDCl ) δ 164.9, 161.6, 155.0,
3
362.2059.
13
1
144.0, 135.7, 133.5, 129.4, 128.8, 127.2, 80.4, 52.4, 50.3,
40.6, 28.4. Characterization data were consistent with previous
literature.
Synthesis of tert-butyl (S)-(1-amino-3-methyl-1-oxobutan-2-
yl)carbamate (21). To a solution of Boc-valine-OH (3 g, 13.8
mmol) and N-methylmorpholine (1.82 mL, 16.5 mmol) in
DME (65 mL) was added isobutyl chloroformate (2.15 mL,
5
3
Synthesis of tert-butyl (S)-(1-(4-(isopropylcarbamoyl) oxazol-
-yl)-2-phenylethyl) carbamate (1c). The reaction was
16.5 mmol) dropwise at 0 °C under inert atmosphere (N ). The
2
2
resulting mixture was stirred at 0 °C for 2 min, and a solution
performed as described in the procedure for compound 1a to
furnish 1c in 100% yield (282 mg). Crude 1c was then purified
by prep-HPLC (70:30 CH
CDCl ) δ 8.02 (s, 1H), 7.19 – 7.12 (m, 3H), 7.01 – 6.87 (m,
2H), 6.57 (d, J = 8.2 Hz, 1H), 5.09 (s, 1H, b), 4.98 (s, 1H, b),
of ammonia (30 % w/w aqueous solution, 5.3 mL) was then
added. The resulting white slurry was vigorously stirred at
room temperature for 1 h and quenched with water. CH Cl
1
3 2
CN:H O). H NMR (400 MHz,
2
2
3
(40 mL) was added, the organic layer was separated, and the
aqueous layer was extracted with CH Cl (3 x 30 mL).
2
2
6
ACS Paragon Plus Environment