Job/Unit: O21725
/KAP1
Date: 26-03-13 17:08:56
Pages: 11
G.-V. Röschenthaler, V. G. Nenajdenko et al.
FULL PAPER
Ethyl {2-[2-(Trifluoromethyl)pyrrolidin-2-yl]-1H-pyrrol-1-yl}acetate 7.13 Hz, 3 H, CH2CH3), 1.44–1.56 (m, 3 H), 1.67–1.74 [m including
(3g): Yellow oil [75% (BF3·Et2O), 81% (TiCl4)]. 1H NMR 1.73 (d, J = 7.23 Hz, 4 H, 3 H, CHCH3)], 1.84–1.98 (m, 2 H), 2.09–
(400 MHz, CDCl3): δ = 1.29 (t, J = 7.13 Hz, 3 H, CH2CH3), 1.81– 2.14 (m, 1 H), 2.78–2.85 (m, 1 H, CH2N), 2.89–2.94 (m, 1 H,
1.99 (m, 3 H), 2.12–2.19 (m, 1 H), 2.32–2.39 (m, 1 H), 3.04–3.17
CH2N), 4.17 (q, J = 7.13 Hz, 2 H, COOCH2CH3), 4.71 (q, J =
(m, 2 H, CH2N), 4.23 (q, J = 7.13 Hz, 2 H, COOCH2CH3), 4.58 7.23 Hz, 1 H, CHCOOEt), 6.11–6.15 (m, 1 H, Ar), 6.72–6.76 (m,
(s, 2 H, CH2COOEt), 6.19–6.22 (m, 1 H, Ar), 6.62–6.63 (t, J = 2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.9 (CH2CH3),
2.52 Hz, 1 H, Ar), 6.68–6.69 (m, 1 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ = 13.9 (CH3), 26.0, 34.0 (CH2-Cq), 47.3
17.9 and 18.0 (CHCH3), 19.9, 25.6, 28.4 and 28.5 (br. s, CH2-Cq),
41.2 (CH2N), 57.1 (CHCOOEt), 59.4 (q, JC,F = 26.4 Hz, C-CF3),
61.4 (COOCH2CH3), 108.4 (Ar), 119.4 and 119.5 (Cq, Ar), 119.7
(CH2N), 50.8 (CH2COOEt), 61.6 (COOCH2CH3), 66.3 (q, JC,F
=
27.3 Hz, C-CF3), 107.8 (Ar), 119.7 (Ar), 122.1 (Ar), 124.4 (Cq, Ar), and 119.8 (Ar), 119.9 and 120.0 (Ar), 126.5 (q, JC,F = 282.9 Hz,
127.5 (q, JC,F = 282.7 Hz, CF3), 168.4 (CO) ppm. 19F NMR CF3), 171.0 (CO) ppm. 19F NMR (280 MHz, CDCl3): δ = –81.1
(280 MHz, CDCl ): δ = –78.6 (CF ) ppm. IR (KBr): ν = 3367,
(CF3) ppm. IR (KBr): ν =
3338, 1728, 1167, 1149 cm–1.
˜
˜
3
3
1753, 1155 cm–1. C13H17F3N2O2 (290.28): calcd. C 53.79, H 5.90, C15H21F3N2O2 (318.34): calcd. C 56.59, H 6.65, N 8.80; found C
N 9.65; found C 53.85, H 5.99, N 9.58.
56.60, H 6.55, N 8.89. [α]1D7 = +11.6 (c = 1.0, CH2Cl2).
Ethyl 2-{2-[2-(Trifluoromethyl)azepan-2-yl]-1H-pyrrol-1-yl}-
propanoate (3l): Yellow oil [60%, diastereomeric mixture (1:1)]. H
Ethyl {2-[2-(Trifluoromethyl)piperidin-2-yl]-1H-pyrrol-1-yl}acetate
1
1
(3h): Yellow oil (62%). H NMR (400 MHz, CDCl3): δ = 1.26 (t,
J = 7.13 Hz, 3 H, CH2CH3), 1.41–1.57 (m, 3 H), 1.65–1.72 (m, 1 NMR (400 MHz, CDCl3): δ = 1.20 (t, J = 7.13 Hz, 3 H, CH2CH3),
H), 1.85–1.92 (m, 1 H), 1.96 (br. s, 1 H, NH), 2.08–2.13 (m, 1 H), 1.29–1.48 (m, 3 H), 1.64–1.78 [m including 1.68 (d, J = 7.34 Hz, 7
2.77–2.84 (m, 1 H, CH2N), 2.87–2.92 (m, 1 H, CH2N), 4.21 (q, J H, 3 H, CHCH3)], 2.04–2.10 (m, 1 H), 2.18–2.24 (m, 1 H), 2.91–
= 7.13 Hz, 2 H, COOCH2CH3), 4.59 (s, 2 H, CH2COOEt), 6.13–
2.93 (m, 2 H, CH2N), 4.14 (q, J = 7.13 Hz, 2 H, COOCH2CH3),
6.15 (m, 1 H, Ar), 6.63–6.66 (m, 2 H, Ar) ppm. 13C NMR 4.66 (q, J = 7.34 Hz, 1 H, CHCOOEt), 6.14–6.16 (m, 1 H, Ar),
(100 MHz, CDCl3): δ = 13.9 (CH3), 19.9, 25.6, 28.5 (br. s, CH2- 6.66–6.68 (m, 1 H, Ar), 6.74–6.76 (m, 1 H, Ar) ppm. 13C NMR
Cq), 41.2 (CH2N), 50.9 (CH2COOEt), 59.4 (q, JC,F = 26.4 Hz, C-
CF3), 61.5 (COOCH2CH3), 108.9 (Ar), 120.0 (Cq, Ar), 121.9 (Ar),
122.0 (Ar), 126.5 (q, JC,F = 282.9 Hz, CF3), 168.4 (CO) ppm. 19F
(100 MHz, CDCl3): δ = 13.9 (CH2CH3), 18.0 and 18.1 (CHCH3),
22.8 and 22.9, 30.0, 33.2 and 33.3, 34.0 (CH2-Cq), 43.7 (CH2N),
57.1 and 57.2 (CHCOOEt), 61.5 (COOCH2CH3), 62.5 (q, JC,F
=
NMR (280 MHz, CDCl ): δ = –81.9 (CF ) ppm. IR (Nujol): ν = 24.9 Hz, C-CF3), 107.7 (Ar), 118.9 (Ar), 119.7 and 119.8 (Ar),
˜
3
3
3345, 1755, 1160 cm–1. C14H19F3N2O2 (304.31): calcd. C 55.26, H
123.8 (Cq, Ar), 128.0 (q, JC,F = 286.5 Hz, CF3), 171.1 (CO) ppm.
6.29, N 9.21; found C 55.26, H 6.35, N 9.10.
19F NMR (280 MHz, CDCl3): δ = –78.75 and 78.76 (CF3) ppm.
IR (Nujol): ν = 3395, 1745, 1205, 1165, 1145 cm–1. C H F N O
2
˜
16 23
3
2
Ethyl
{2-[2-(Trifluoromethyl)azepan-2-yl]-1H-pyrrol-1-yl}acetate
(332.36): calcd. C 57.82, H 6.98, N 8.43; found C 57.94, H 7.00, N
1
(3i): Yellow oil (65%). H NMR (400 MHz, CDCl3): δ = 1.27 (t, J
= 7.13 Hz, 3 H, CH2CH3), 1.31–1.52 (m, 3 H), 1.67–1.80 (m, 4 H),
8.30. [α]2D5 = +10.8 (c = 1.0, CH2Cl2).
2.04–2.12 (m, 1 H), 2.20–2.26 (m, 1 H), 2.93–2.95 (m, 2 H, CH2N), 2-{2-[2-(Trifluoromethyl)pyrrolidin-2-yl]-1H-pyrrol-1-yl}propanoic
4.21 (q,
J
=
7.13 Hz,
2
H, COOCH2CH3), 4.56 (s,
2
H, Acid (3m): Yellow liquid [73%, diastereomeric mixture (1:1)]. 1H
NMR (400 MHz, CDCl3): δ = 1.63 (t, J = 5.92 Hz, 3 H, CHCH3),
1.84–2.03 (m, 2 H), 2.23–2.41 (m, 2 H), 3.07–3.17 (m, 2 H, CH2N),
CH2COOEt), 6.19–6.21 (t, J = 2.52 Hz, 1 H, Ar), 6.60–6.62 (t, J =
1.97 Hz, 1 H, Ar), 6.68–6.70 (m, 1 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ = 13.9 (CH3), 22.7, 29.9, 33.2, 33.9, (CH2- 4.59 (m, 1 H, CHCOOH), 6.09–6.14 (m, 1 H, Ar), 6.65–6.70 (m, 1
Cq), 43.6 (CH2N), 50.8 (CH2COOEt), 61.5 (COOCH2CH3), 62.4
(q, JC,F = 25.3 Hz, C-CF3), 108.1 (Ar), 120.8 (Ar), 121.8 (Ar), 124.6
(Cq, Ar), 127.9 (q, JC,F = 286.5 Hz, CF3), 168.4 (CO) ppm. 19F
H, Ar), 6.84–6.87 (m, 1 H, Ar), 8.36 (br. s, 2 H, NH2+) ppm. 13C
NMR (100 MHz, CDCl3): δ = 18.4 and 18.5 ppm (CHCH3), 24.6
and 24.7, 32.0 (CH2-Cq), 46.4 and 46.5 (CH2N), 58.3 and 58.5
NMR (280 MHz, CDCl ): δ = –78.7 (CF ) ppm. IR (Nujol): ν = (CHCOOH), 67.4 (q, JC,F = 29.1 Hz, C-CF3), 106.9 (Ar), 118.9
˜
3
3
3390, 1755, 1145, 1149 cm–1. C15H21F3N2O2 (318.34): calcd. C
(Ar), 119.2 and 119.3 (Cq, Ar), 120.4 and 120.5 (Ar), 126.2 and
126.3 (q, JC,F = 282.0 Hz, JC,F = 283.1 Hz, CF3), 175.7 (br. s,
COOH) ppm. 19F NMR (280 MHz, CDCl3): δ = –77.25 and 77.29
56.59, H 6.65, N 8.80; found C 56.30, H 6.50, N 8.83.
Ethyl
2-{2-[2-(Trifluoromethyl)pyrrolidin-2-yl]-1H-pyrrol-1-yl}-
(CF ) ppm. IR (KBr): ν = 3381 (br. s), 1714, 1155 cm–1
.
˜
3
propanoate (3j): Yellow oil [69% (BF3·Et2O), 73% (TiCl4), dia-
stereomer mixture (1:1)]. 1H NMR (400 MHz, CDCl3): δ = 1.25 (t,
J = 7.12 Hz, 3 H, CH2CH3), 1.71 (d, J = 7.23 Hz, 3 H, CHCH3),
1.82–1.89 (m, 2 H), 1.93–2.01 (m, 1 H), 2.12–2.18 (m, 1 H), 2.32–
2.39 (m, 1 H), 3.04–3.10 (m, 1 H, CH2N), 3.13–3.19 (m, 1 H,
CH2N), 4.18 (q, J = 7.12 Hz, 2 H, COOCH2CH3), 4.69 (q, J =
7.23 Hz, 1 H, CHCOOEt), 6.18–6.20 (m, 1 H, Ar), 6.70–6.72 (m,
1 H, Ar), 6.75–6.77 (m, 1 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 13.9 (CH2CH3), 18.1 (CHCH3), 25.6, 33.9 and 34.0
(CH2-Cq), 42.3 (CH2N), 57.1 (CHCOOEt), 61.5 (COOCH2CH3),
66.4 (q, JC,F = 27.3 Hz, C-CF3), 107.3 (Ar), 117.7 (Ar), 119.9 and
120.0 (Ar), 123.9 (Cq, Ar), 127.5 (q, JC,F = 283.1 Hz, CF3), 170.9
C12H15F3N2O2·H2O (276.26): calcd. C 48.98, H 5.82, N 9.52; found
C 48.97, H 5.67, N 9.18. [α]1D7 = +12.0 (c = 0.5, CH2Cl2).
2-{3-[2-(Trifluoromethyl)pyrrolidin-2-yl]-1H-pyrrol-1-yl}ethanol
(3n): Yellow oil (64%). 1H NMR (400 MHz, CDCl3): δ = 1.75–1.82
(m, 1 H), 1.89–1.96 (m, 1 H), 2.09–2.14 (m, 1 H), 2.28–2.33 (m, 1
H), 2.83 (br. s, 2 H, NH and OH), 2.93–2.97 (m, 1 H, CH2N),
3.02–3.06 (m, 1 H, CH2N), 3.76 (t, J = 5.23 Hz, 2 H, CH2CH2),
3.90 (t, J = 5.23 Hz, 2 H, CH2CH2), 6.11–6.12 (m, 1 H, Ar), 6.63–
6.64 (m, 1 H, Ar), 6.68 (t, J = 2.02 Hz, 1 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ = 25.8, 33.8 (CH2-Cq), 47.3 (CH2N), 52.2
(CH2CH2), 62.16 (CH2CH2), 66.3 (q, JC,F = 27.3 Hz, C-CF3), 107.0
(CO) ppm. 19F NMR (280 MHz, CDCl3): δ = –77.8 (CF3) ppm. IR (Ar), 118.8 (Ar), 121.4 (Ar), 123.3 (Cq, Ar), 127.4 (q, JC,F
=
(KBr): ν = 3373, 1741, 1190, 1151 cm–1. C H F N O (304.31): 283.1 Hz, CF3) ppm. 19F NMR (280 MHz, CDCl3): δ = –77.4
˜
14 19
3
2
2
calcd. C 55.26, H 6.29, N 9.21; found C 55.36, H 6.33, N 9.17.
(CF ) ppm. IR (KBr): ν = 3325, 1151, 1082, 783, 731 cm–1. HRMS
˜
3
[α]2D5 = +13.2 (c = 1.0, CH2Cl2).
(ESI): calcd. for C11H15F3N2O [M + H] 249.1209; found 249.1221.
Ethyl
2-{2-[2-(Trifluoromethyl)piperidin-2-yl]-1H-pyrrol-1-yl}- 2-{2-[2-(Trifluoromethyl)pyrrolidin-2-yl]-1H-pyrrol-1-yl}ethanol
propanoate (3k): Yellow solid [75%, diastereomeric mixture (1:1)];
(2n): Yellow solid (14 %); m.p. 92–94 °C. 1H NMR (400 MHz,
m.p. 46–48 °C. 1H NMR (400 MHz, CDCl3): δ = 1.23 (t, J = CDCl3): δ = 1.84–1.91 (m, 1 H), 1.92–1.99 (m, 1 H), 2.45–2.53 (m,
8
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