Yellowish oil (13.8 g, 89 %).
1H NMR (CDCl3, 400 MHz): δ = 0.89−0.94 (m, 2 H, CH2), 1.04−1.08 (m, 2 H, CH2), 1.31 (t, J = 7.0 Hz,
3 H, CH2CH3), 1.57−1.63 (m, 1 H, CH), 4.23 (q, J = 7.0 Hz, 2 H, CH2CH3), 5.64 (s, 1 H, CH), 7.27 (t, 2JH−F
= 54.0 Hz, 1 H, CHF2), 10.99 (br s, 1 H, NH) ppm.
13C NMR (CDCl3, 100 MHz): δ = 9.1 (2×CH2), 14.0 (CH2CH3), 15.8 (CH), 60.9 (CH2CH3), 96.3 (t, 3JC−F
= 9.5 Hz, CH), 108.5 (t, 1JC−F = 242.0 Hz, CHF2), 146.9 (t, 2JC−F = 23.5 Hz, C−CHF2), 168.6 (CO2Et), 172.1
(CO) ppm.
19F NMR (CDCl3, 376 MHz,): δ = − 122.51 (d, 2JH−F = 54.0 Hz, CHF2) ppm.
MS: m/z = 234 [M + H]+.
Anal. Calcd for C10H13F2NO3: C, 51.50; H, 5.62; N, 6.01. Found: C, 51.41; H, 5.59; N, 5.89.
4.2.3. Ethyl 3-[(2,2-dimethylpropanoyl)amino]-4,4-difluorobut-2-enoate (18c)
Yellowish oil (11.1 g, 75 %).
1H NMR (CDCl3, 400 MHz): δ = 1.27 (s, 9 H, C(CH3)3), 1.30 (t, J = 7.0 Hz, 3 H, CH2CH3), 4.22 (q, J =
7.0 Hz, 2 H, CH2CH3), 5.66 (s, 1 H, CH), 7.29 (t, 2JH−F = 54.2 Hz, 1 H, CHF2), 11.07 (br s, 1 H, NH) ppm.
13C NMR (CDCl3, 100 MHz): δ = 14.0 (CH2CH3), 27.2 (C(CH3)3), 40.0 (C(CH3)3), 60.9 (CH2CH3), 97.0
3
1
2
(t, JC−F = 9.5 Hz, CH), 108.7 (t, JC−F = 241.4 Hz, CHF2), 147.3 (t, JC−F = 23.5 Hz, C−CHF2), 168.7
(CO2Et), 177.2 (CO) ppm.
19F NMR (CDCl3, 376 MHz,): δ = − 122.74 (d, 2JH−F = 54.0 Hz, CHF2) ppm.
MS: m/z = 250 [M + H]+.
Anal. Calcd for C11H17F2NO3: C, 53.01; H, 6.87; N, 5.62. Found: C, 52.93; H, 6.92; N, 5.69.
4.2.4. Ethyl 3-benzoylamino-4,4-difluorobut-2-enoate (18d)
White solid (13.5 g, 82 %) mp 65 °C.
1H NMR (CDCl3, 400 MHz): δ = 1.36 (t, J = 6.8 Hz, 3 H, CH2CH3), 4.30 (q, J = 6.8 Hz, 2 H, CH2CH3),
5.82 (s, 1 H, CH), 7.51 (t, 2JH−F = 53.7 Hz, 1 H, CHF2), 7.53 (t, J = 7.8 Hz, 2 H, 2×HPh), 7.61 (t, J = 7.8 Hz, 1
H, HPh), 7.99 (d, J = 7.8 Hz, 2 H, 2×HPh), 11.83 (br s, 1 H, NH) ppm.
13C NMR (CDCl3, 100 MHz): δ = 14.1 (CH2CH3), 61.1 (CH2CH3), 97.7 (t, JC−F = 10.3 Hz, CH), 108.8
3
1
2
(t, JC−F = 242.1 Hz, CHF2), 127.8 (2×CHPh), 129.0 (2×CHPh), 132.5 (CPh), 133.0 (CHPh), 147.3 (t, JC−F
=
23.5 Hz, C−CHF2), 164.7, 169.0 ppm.
19F NMR (CDCl3, 376 MHz,): δ = − 122.39 (d, 2JH−F = 54.0 Hz, CHF2) ppm.
MS: m/z = 270 [M + H]+.
Anal. Calcd for C13H13F2NO3: C, 57.99; H, 4.87; N, 5.20. Found: C, 58.04; H, 4.91; N, 5.18.
4.2.5. Ethyl 4,4-difluoro-3-[(4-methoxybenzoyl)amino]but-2-enoate (18e)
White solid (12.1 g, 67 %) mp 63ꢀ°C.
1H NMR (CDCl3, 400 MHz): δ = 1.36 (t, J = 7.0 Hz, 3 H, CH2CH3), 3.89 (s, 3 H, OMe), 4.29 (q, J = 7.0
Hz, 2 H, CH2CH3), 5.78 (s, 1 H, CH), 7.00 (d, J = 8.8 Hz, 2 H, 2×HAr), 7.51 (t, 2JH−F = 54.2 Hz, 1 H, CHF2),
7.96 (d, J = 8.8 Hz, 2 H, 2×HAr), 11.76 (br s, 1 H, NH) ppm.
3
13C NMR (CDCl3, 100 MHz): δ = 14.2 (CH2CH3), 55.5 (OMe), 61.0 (CH2CH3), 97.0 (t, JC−F = 9.5 Hz,
1
2
CH), 108.8 (t, JC−F = 242.1 Hz, CHF2), 114.2 (2×CHAr), 124.8 (CAr), 129.9 (2×CHAr), 147.6 (t, JC−F = 23.5
Hz, C−CHF2), 163.4, 164.2, 169.1 ppm.
19F NMR (CDCl3, 376 MHz,): δ = − 122.31 (d, 2JH−F = 54.0 Hz, CHF2) ppm.
MS: m/z = 300 [M + H]+.
Anal. Calcd for C14H15F2NO4: C, 56.19; H, 5.05; N, 4.68. Found: C, 56.09; H, 4.97; N, 4.75.
4.2.6. Ethyl 4,4-difluoro-3-[(4-nitrobenzoyl)amino]but-2-enoate (18f)
Yellow solid (11.6 g, 61 %) mp 78 °C.
1H NMR (DMSO[D6], 500 MHz): δ = 1.23 (t, J = 7.1 Hz, 3 H, CH2CH3), 4.20 (q, J = 7.1 Hz, 2 H,
CH2CH3), 5.88 (s, 1 H, CH), 7.29 (t, 2JH−F = 54.1 Hz, 1 H, CHF2), 8.13 (d, J = 8.8 Hz, 2 H, 2×HAr), 8.41 (d, J
= 8.8 Hz, 2 H, 2×HAr), 11.34 (s, 1 H, NH) ppm.
3
13C NMR (DMSO[D6], 125 MHz): δ = 14.0 (CH2CH3), 61.0 (CH2CH3), 103.0 (t, JC−F = 9.0 Hz, CH),
1
2
109.8 (t, JC−F = 240.8 Hz, CHF2), 124.2 (2×CHAr), 129.2 (2×CHAr), 138.0 (CAr), 144.2 (t, JC−F = 23.4 Hz,
C−CHF2), 150.0 (C−NO2), 162.9, 166.8 ppm.
19F NMR (DMSO[D6], 376 MHz,): δ = − 121.22 (d, 2JH−F = 53.5 Hz, CHF2) ppm.
MS: m/z = 315 [M + H]+.
Anal. Calcd for C13H12F2N2O5: C, 49.69; H, 3.85; N, 8.91. Found: C, 49.78; H, 3.77; N, 9.02.