The Journal of Organic Chemistry
Article
152.52, 140.20, 135.59, 128.44, 128.25, 128.09, 94.60, 67.37, 51.01.
HRMS (ESI) (m/z): ([M − H]−) calcd for C12H13NO4, 234.0767;
found, 234.0767; and 2nd eluting compound (E)-methyl 3-
(((benzyloxy)carbonyl)amino)acrylate 14E (3.6 g, 54.8%) as a white
crystalline solid: 1H NMR (CDCl3, 500 MHz): δ 7.81 (t, J = 13.1 Hz,
1H), 7.47−7.29 (m, 5H), 6.94 (d, J = 12.0 Hz, 1H), 5.35 (d, J = 14.1 Hz,
1H), 5.19 (s, 2H), 3.69 (s, 3H); 1H (DMSO-d6, 500 MHz): δ 10.61−
10.38 (m, 1H), 7.65 (dd, J = 14.0, 11.1 Hz, 1H), 7.48−7.14 (m, 5H),
5.40 (d, J = 14.0 Hz, 1H), 5.18 (s, 2H), 3.61 (s, 3H); 13C{1H} NMR
(DMSO-d6, 125 MHz): δ 167.2, 153.4, 140.6, 135.8, 128.5, 128.3,
128.2, 98.2, 67.0, 50.9. HRMS (ESI) (m/z): ([M − H]−) calcd for
C12H13NO4, 234.0767, found, 234.0768.
Methyl (E)-3-((tert-Butoxycarbonyl)amino)acrylate (17E) and
Methyl (Z)-3-((tert-Butoxycarbonyl)amino)acrylate (17Z).14 To a
250 mL 1-neck flask, with a stir bar and an air condenser under N2, are
added methyl 2-(triphenylphosphoranylidene)acetate (34.6 g, 103
mmol), tert-butyl formylcarbamate 13 (7.5 g, 51.7 mmol), and toluene
(100 mL, anhydrous). The reaction is heated at 90 °C (internal
temperature) for 18 h. The reaction is cooled to ambient temperature
and concentrated in vacuo. The residue is dry loaded onto silica gel
(dissolved in DCM, added silica gel, and concentrated to dryness). The
silica is packed into a dry load cartridge, placed on top of a silica gel
column (ISCO 120 g gold), and chromatographed (conditioned with
hexanes, eluted with 1 CV hexanes then gradient eluted with 40%
EtOAc/hexanes over 6 CV, and then held for 6 CV) to give the 1st
eluting compound (Z)-methyl 3-((tert-butoxycarbonyl)amino)acrylate
17Z (3.729 g, 35.9%) as an oil: 1H NMR (CDCl3, 500 MHz): δ 9.56 (s,
1H), 7.23 (t, J = 12.0 Hz, 1H), 4.98 (d, J = 8.9 Hz, 1H), 3.68 (s, 3H),
1.46 (s, 9H); 1H NMR (DMSO-d6, 500 MHz): δ 9.53 (d, J = 11.8 Hz,
1H), 7.27 (dd, J = 11.8, 8.8 Hz, 1H), 5.05 (d, J = 8.9 Hz, 1H), 3.64 (s,
3H), 1.46 (s, 9H); 13C{1H} NMR (DMSO-d6, 125 MHz): δ 168.7,
151.2, 140.4, 93.4, 81.6, 50.8, 27.5. HRMS (ESI) (m/z): ([M − H]−)
calcd for C9H15NO4, 200.0923; found, 200.0921; and the 2nd eluting
compound (E)-methyl 3-((tert-butoxycarbonyl)amino)acrylate 17E
(5.857 g, 56.3%) as a white solid, which is spectroscopically identical
to the material previously reported herein or in the literature:10 1H
NMR (CDCl3, 500 MHz): δ 7.78 (t, J = 13.0 Hz, 1H), 6.73 (d, J = 12.3
Hz, 1H), 5.29 (d, J = 14.0 Hz, 1H), 3.69 (s, 3H), 1.47 (s, 9H); 1H NMR
(DMSO-d6, 500 MHz): δ 10.12 (s, 1H), 7.60 (dd, J = 14.0, 11.2 Hz,
1H), 5.34 (d, J = 14.0 Hz, 1H), 3.59 (s, 3H), 1.44 (s, 9H); 13C{1H}
NMR (DMSO-d6, 125 MHz): δ 167.3, 152.2, 140.9, 97.2, 80.9, 50.7,
27.7. HRMS (ESI) (m/z): ([M − H]−) calcd for C9H15NO4, 200.0923;
found, 200.0923.
Ethyl (E)-3-((tert-Butoxycarbonyl)amino)acrylate (18E) and Ethyl
(Z)-3-((tert-Butoxycarbonyl)amino)acrylate (18Z).14 To a 40 mL vial,
with a stir bar, are added tert-butyl formylcarbamate 13 (2.03 g, 13.95
mmol), ethyl (triphenylphosphoranylidene)acetate (7.29 g, 20.93
mmol), and then toluene (15 mL, anhydrous). The reaction is heated
at 95 °C for 18 h. The reaction is then cooled to ambient temperature
and loaded directly onto a 40 g ISCO gold column that is then placed on
top of an 80 g ISCO gold (conditioned with hexanes, eluted with 2 CV
hexanes then gradient eluted with 100% MTBE over 8 CV, and then
held for 6 CV) to give the 1st eluting compound ethyl (Z)-3-((tert-
butoxycarbonyl)amino)acrylate 18Z (1.35 g, 45.0%) as a clear, colorless
oil: 1H NMR (CDCl3, 500 MHz): δ 9.60 (s, 1H), 7.21 (t, J = 10.5 Hz,
1H), 4.97 (d, J = 8.9 Hz, 1H), 4.14 (d, J = 7.2 Hz, 2H), 1.46 (s, 9H), 1.26
(t, J = 7.1 Hz, 3H); 1H NMR (DMSO-d6, 500 MHz): δ 9.57 (d, J = 11.7
Hz, 1H), 7.26 (dd, J = 11.7, 8.8 Hz, 1H), 5.04 (d, J = 8.9 Hz, 1H), 4.11
(q, J = 7.1 Hz, 2H), 1.46 (s, 9H), 1.21 (t, J = 7.1 Hz, 3H); 13C{1H} NMR
(DMSO-d6, 125 MHz): δ 168.4, 151.2, 140.4, 93.7, 81.5, 59.5, 27.5,
14.0. HRMS (ESI) (m/z): ([M + H]+) calcd for C10H17NO4, 216.1236;
found, 216.1238; and the 2nd eluting compound ethyl (E)-3-((tert-
butoxycarbonyl)amino)acrylate 18E (1.52 g, 50.9%) as a white solid:
1H NMR (CDCl3, 500 MHz): δ 7.77 (t, J = 13.1 Hz, 1H), 6.83 (d, J =
Ethyl (E)-3-(((Benzyloxy)carbonyl)amino)acrylate (15E)13 and
Ethyl (Z)-3-(((Benzyloxy)carbonyl)amino)acrylate (15Z). To a 40
mL vial, with a stir bar, are added benzyl formylcarbamate 12 (2.5 g,
13.95 mmol), ethyl(triphenylphosphoranylidene)acetate (7.29 g, 20.93
mmol), and then toluene (15 mL, anhydrous). The reaction is heated at
95 °C for 18 h. The reaction is then cooled to ambient temperature and
loaded directly onto a 40 g ISCO gold column that is then placed on top
of an 80 g ISCO gold (conditioned with hexanes, eluted with 2 CV
hexanes then gradient eluted with 100% MTBE over 8 CV, and then
held for 6 CV) to give the 1st eluting compound ethyl (Z)-3-
(((benzyloxy)carbonyl)amino)acrylate 15Z (1.62 g, 46.6%) as a clear,
colorless oil: 1H NMR (CDCl3, 500 MHz): δ 9.84 (s, 1H), 7.52−7.01
(m, 6H), 5.19 (s, 2H), 5.04 (d, J = 8.9 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H),
1.26 (t, J = 7.1 Hz, 3H); 1H NMR (DMSO-d6, 500 MHz): δ 9.82 (d, J =
11.6 Hz, 1H), 7.46−7.22 (m, 6H), 5.21 (s, 2H), 5.10 (d, J = 8.9 Hz, 1H),
4.10 (q, J = 7.1 Hz, 1H), 1.19 (t, J = 7.1 Hz, 3H); 13C{1H} NMR
(DMSO-d6, 125 MHz): δ 168.2, 152.5, 140.2, 135.6, 128.4, 128.2,
128.1, 94.9, 67.3, 59.7, 14.0. HRMS (ESI) (m/z): ([M − H]−) calcd for
C13H15NO4, 248.0923; found, 248.0923; and the 2nd eluting
compound ethyl (E)-3-(((benzyloxy)carbonyl)amino) acrylate 15E
(1.65 g, 47.4%) as a white solid: 1H NMR (CDCl3, 500 MHz): δ 7.80 (t,
J = 13.1 Hz, 1H), 7.36−7.33 (d, J = 4.4 Hz, 5H), 6.97 (d, J = 12.1 Hz,
1H), 5.34 (d, J = 14.0 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H), 1.25 (t, J = 7.1
Hz, 3H); 1H (DMSO-d6, 500 MHz): δ 10.50 (s, 1H), 7.63 (dd, J = 14.0,
11.1 Hz, 1H), 7.51−6.98 (m, 5H), 5.38 (d, J = 14.0 Hz, 1H), 5.18 (s,
2H), 4.07 (q, J = 7.1 Hz, 2H), 1.18 (t, J = 7.1 Hz, 3H); 13C{1H} NMR
(DMSO-d6, 125 MHz): δ 166.7, 153.4, 140.4, 135.8, 128.5, 128.3,
128.2, 98.6, 67.0, 59.3, 14.2. HRMS (ESI) (m/z): ([M − H]−) calcd for
C13H15NO4, 248.0923; found, 248.0924.
tert-Butyl (E)-3-(((Benzyloxy)carbonyl)amino)acrylate (16E)10f
and tert-Butyl (Z)-3-(((Benzyloxy)carbonyl)amino)acrylate (16Z).10f
To a 40 mL vial, with a stir bar, are added benzyl formylcarbamate 12
(2.5 g, 13.95 mmol), (tert-butoxycarbonylmethylene)-
triphenylphosphorane (7.88 g, 20.93 mmol), and then toluene (15
mL, anhydrous). The reaction is heated at95 °C for 18 h. The reaction is
then cooled to ambient temperature and loaded directly onto a 40 g
ISCO gold column that is then placed on top of an 80 g ISCO gold
(conditioned with hexanes, eluted with 2 CV hexanes then gradient
eluted with 100% MTBE over 8 CV, and then held for 6 CV) to give the
1st eluting compound tert-butyl (Z)-3-(((benzyloxy)carbonyl)amino)-
acrylate 16Z (1.98 g, 51.2%) as a clear, colorless oil: 1H NMR (CDCl3,
500 MHz): δ 9.96−9.80 (m, 1H), 7.37−7.31 (m, 5H), 7.19 (t, J = 10.1
Hz, 1H), 5.18 (s, 2H), 4.96 (d, J = 8.6 Hz, 1H), 1.59−1.33 (m, 9H); 1H
NMR (DMSO-d6, 500 MHz): δ 9.82 (d, J = 11.5 Hz, 1H), 7.47−7.33
(m, 5H), 7.25(dd, J= 11.6, 8.9Hz, 1H), 5.20(s, 2H), 5.01(d, J= 8.9 Hz,
1H), 1.43 (s, 9H); 13C{1H} NMR (DMSO-d6, 125 MHz): δ 168.0,
152.5, 139.6, 135.6, 128.4, 128.2, 128.1, 96.5, 80.3, 67.3, 27.8. HRMS
(ESI) (m/z): ([M − H]−) calcd for C15H19NO4, 276.1236; found,
276.1236; and the 2nd eluting compound (E)-3-(((benzyloxy)-
12.3 Hz, 1H), 5.27 (d, J = 14.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 1.47 (s,
9H), 1.24 (t, J = 7.1 Hz, 3H); 1H NMR (DMSO-d6, 500 MHz): δ 7.59
(dd, J = 14.0, 11.3 Hz, 1H), 5.32 (d, J = 14.0 Hz, 1H), 4.05 (q, J = 7.1 Hz,
2H), 1.44 (s, 9H), 1.18 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (DMSO-d6,
125 MHz): δ 166.9, 152.3, 140.7, 97.5, 80.9, 59.1, 27.8, 14.2. HRMS
(ESI) (m/z): ([M + H]+) calcd for C10H17NO4, 216.1236; found,
216.1234.
tert-Butyl (E)-3-((tert-Butoxycarbonyl)amino)acrylate (19E) and
tert-Butyl (Z)-3-((tert-Butoxycarbonyl)amino)acrylate (19Z).10d To a
40 mL vial, with a stir bar, are added tert-buty formylcarbamate 13 (2.03
g, 13.95 mmol), (tert-butoxycarbonylmethylene)triphenylphosphorane
(7.88 g, 20.93 mmol), and then toluene (15 mL, anhydrous). The
reaction is heated at 95 °C for 18 h. The reaction is then cooled to
ambient temperature and loaded directly onto a 40 g ISCO gold column
that is then placed on top of an 80 g ISCO gold (conditioned with
hexanes, eluted with 2 CV hexanes then gradient eluted with 100%
MTBE over 8 CV, and then held for 6 CV) to give the 1st eluting
compound tert-Butyl (Z)-3-((tert-butoxycarbonyl)amino)acrylate 19Z
1
carbonyl)amino)acrylate 16E (1.74 g, 45.0%) as a white solid: H
NMR(CDCl3, 500 MHz): δ 7.69(dd, J = 14.0, 12.0 Hz, 1H), 7.39−7.30
(m, 5H), 6.76 (s, 1H), 5.27 (d, J = 14.1 Hz, 1H), 5.18 (s, 2H), 1.45 (s,
9H); 1H NMR (DMSO-d6, 500 MHz): δ 10.41 (s, 1H), 7.53 (dd, J =
14.0, 11.1 Hz, 1H), 7.45−7.22 (m, 5H), 5.28 (d, J = 14.0 Hz, 1H), 5.17
(s, 2H), 1.41 (s, 9H); 13C{1H} NMR (DMSO-d6, 125 MHz): δ 166.1,
153.4, 139.7, 135.8, 128.5, 128.3, 128.2, 100.4, 79.0, 66.9, 27.9. HRMS
(ESI) (m/z): ([M − H]−) calcd for C15H19NO4, 276.1236; found,
276.1236.
G
J. Org. Chem. XXXX, XXX, XXX−XXX