W. Wan, J. Hou, H. Jiang, Z. Yuan, G. Ma, G. Zhao, J. Hao
FULL PAPER
NMR (500 MHz, CDCl3): δ = 7.07 (t, J = 7.5 Hz, 1 H, ArH), 6.60
(d, J = 7.5 Hz, 1 H, ArH), 6.46 (d, J = 8.0 Hz, 2 H, ArH), 4.06–
3.97 (m, 1 H, CH), 3.65 (s, 3 H, OCH3), 3.61 (d, J = 10 Hz, 1 H,
29.8, 24.5 ppm. 19F NMR (470 MHz, CDCl3): δ = –76.26 (d, J =
9.4 Hz, CF ), –126.27 (m, ArF) ppm. IR (KBr): ν = 3392, 3039,
˜
3
2955, 1729, 1614, 1511, 1441, 1168, 1124, 824, 769 cm–1.
NH), 2.54–2.47 (m, 2 H, CH2), 2.28 (s, 3 H, CH3), 2.24–2.17 (m, C12H13F4NO2 (279.1): calcd. C 51.62, H 4.69, N 5.02; found C
1 H, CH2), 1.93–1.85 (m, 1 H, CH2) ppm. 13C NMR (125 MHz, 51.41, H 4.55, N 5.31.
CDCl3): δ = 173.4, 146.4, 139.3, 129.3, 126.1 (q, 1JC,F = 282.5 Hz),
5,5,5-Trifluoro-4-(p-fluorophenylamino)pentan-1-ol (4f): Compound
2
119.8, 114.2, 110.4, 55.0 (q, JC,F = 28.75 Hz), 51.9, 29.7, 24.5,
4f (0.070 g) was obtained as a yellow oil in 14% yield by flash
21.6 ppm. 19F NMR (470 MHz, CDCl3): δ = –76.26 (d, J = 9.4 Hz,
column chromatography (hexane/ethyl acetate, 1:1) on silica gel. 1H
CF ) ppm. IR (KBr): ν = 3390, 2954, 1733, 1608, 1525, 1491, 1259,
˜
3
NMR (500 MHz, CDCl3): δ = 6.90 (t, 2 H, ArH), 6.55–6.62 (m, 2
H, ArH), 3.83 (m, 1 H, CH), 3.69 (t, 2 H, CH2), 2.44 (br., 2 H,
NH, OH), 2.04–1.99 (m, 1 H, CH2), 1.76–1.17 (m, 1 H, CH2), 1.82–
1.65 (m, 2 H, CH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 156.6
1168, 1124, 772, 693 cm–1. C13H16F3NO2 (275.1): calcd. C 56.72,
H 5.86, N 5.09; found C 56.57, H 5.68, N 5.30.
4-(m-Toluidino)-5,5,5-trifluoropentan-1-ol (4d): Compound 4d
1
4
1
(d, JC,F = 236.25 Hz), 143.0 (d, JC,F = 1.25 Hz), 125.2 (q, JC,F
(0.094 g) was obtained as a yellow oil in 19% yield by flash column
2
3
1
= 281 Hz), 116.0 (d, JC,F = 22.5 Hz),114.7 (d, JC,F = 7.5 Hz),
chromatography (hexane/ethyl acetate, 1:1) on silica gel. H NMR
62.2, 56.8 (q, JC,F = 28.75 Hz), 28.5, 26.3 ppm. 19F NMR
2
(500 MHz, CDCl3): δ = 7.34 (t, J = 7.5 Hz, 1 H, ArH), 7.19–7.12
(d, J = 7.5 Hz, 1 H, ArH), 6.78–6.74 (d, J = 8.0 Hz, 2 H, ArH),
4.16 (m, 1 H, CH), 3.73 (m, 2 H, CH2), 3.69 (m, 2 H, CH2), 2.38
(s, 3 H, CH3), 2.12–2.04 (m, 1 H, CH2), 1.85–1.76 (m, 1 H, CH2),
1.76–1.67 (m, 2 H, CH2) ppm. 13C NMR (125 MHz, CDCl3): δ =
144.5, 130.6, 127.4, 126.3 (q, 1JC,F = 282.5 Hz), 122.9, 118.3, 110.8,
(470 MHz, CDCl3): δ = –76.01 (d, J = 9.4 Hz, 3 F), 126.08 (m,
ArF) ppm. IR (neat): ν = 3445, 2984, 2937, 1733, 1041, 1565, 127,
˜
1026, 860, 776 cm–1. M.p. 113.4–113.8 °C. MS: m/z = 266.00 [M]+.
C11H13F4NO (251.1): calcd. C 52.59, H 5.22, N 5.58; found C
52.68, H 5.45, N 5.45.
2
62.0, 55.4 (q, JC,F = 28.75 Hz), 28.4, 26.3, 17.5 ppm. 19F NMR
General Procedure for the Synthesis of Trifluoromethylated N-Aryl
Lactams 9: To a solution of 3 (1.0 mmol) in THF (10 mL) was
added NaH (1.1 mmol) under a nitrogen atmosphere at room tem-
perature. After the reaction mixture was stirred for 2 h, the mixture
was poured into saturated aqueous NH4Cl solution and extracted
with AcOEt (4ϫ30 mL). The EtOAc extract was successively
washed with saturated aqueous NaHCO3 solution and brine, dried
with MgSO4, concentrated. Purification of the residue by column
chromatography gave lactam 9.
(470 MHz, CDCl ): δ = –79.71 (s, CF ) ppm. IR (KBr): ν = 3419,
˜
3
3
3303, 2921, 1615, 1563, 1493, 1136, 781, 691 cm–1. C12H16F3NO
(247.1): calcd. C 58.29, H 6.52, N 5.66; found C 58.35, H 6.35, N,
5.39.
Methyl 4-(o-Toluidino)-5,5,5-trifluoropentanoate (3e): Compound
3e (0.347 g) was obtained as a yellow oil in 63% yield by flash
column chromatography (hexane/ethyl acetate, 4:1) on silica gel. 1H
NMR (500 MHz, CDCl3): δ = 7.11 (t, J = 8.0 Hz, 1 H, ArH), 7.07
(d, J = 7.5 Hz, 1 H, ArH), 6.73 (t, J = 7.5 Hz, 1 H, ArH), 6.67 (d,
J = 8.0 Hz, 1 H, ArH), 4.12 (br., 1 H, CH), 3.64 (s, 3 H, OCH3),
3.53 (br., 1 H, NH), 2.52–2.49 (m, 2 H, CH2), 2.27–2.17 (m, 1 H,
CH2), 2.17 (s, 3 H, ArCH3), 1.98–1.93 (m, 1 H, CH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 173.5, 144.4, 130.8, 127.3, 126.1 (q,
1-Phenyl-5-(trifluoromethyl)pyrrolidin-2-one (9a): Compound 9a
(0.215 g) was obtained as a colorless solid in 94% yield by flash
column chromatography (hexane/ethyl acetate, 2:1) on silica gel. 1H
NMR (500 MHz, CDCl3): δ = 7.42 (t, J = 7.5 Hz, 2 H, ArH), 7.34–
7.30 (m, 3 H, ArH), 7.29 (d, J = 7.5 Hz, 2 H, ArH), 4.65–4.59 (m,
1 H, CF3CH), 2.83–2.76 (m, 1 H, CH), 2.60–2.45 (m, 2 H, CH2),
2.35–2.29 (m, 1 H, CH2) ppm. 13C NMR (125 MHz, CDCl3): δ =
2
1JC,F = 282.5 Hz), 122.4, 118.6, 110.9, 54.9 (q, JC,F = 28.75 Hz),
51.9, 29.9, 24.7, 17.6 ppm. 19F NMR (470 MHz, CDCl3): δ =
1
–76.26 (d, J = 4.7 Hz, CF ) ppm. IR (KBr): ν = 3419, 2954, 1735,
˜
3
174.5, 137.1, 129.3, 128.7, 125.3 (q, JC,F = 282.5 Hz), 121.9 (2 C),
1608, 1521, 1255, 1124, 748 cm–1. C13H16F3NO2 (275.1): calcd. C
2
61.0 (q, JC,F = 28.1 Hz), 29.7, 19.4 ppm. 19F NMR (470 MHz,
56.72, H 5.86, N 5.09; found C 56.90, H, 5.59, N 5.32.
CDCl ): δ = –75.13 (d, J = 4.7 Hz, CF ) ppm. IR (KBr): ν = 3064,
˜
3
3
2941, 1699, 1593, 1500, 1457, 762, 697 cm–1. C11H10F3NO (229.2):
4-(o-Toluidino)-5,5,5-trifluoropentan-1-ol (4e): Compound 4e
calcd. C 57.64, H 4.40, N 6.11; found C 57.87, H 4.41, N 6.24.
(0.094 g) was obtained as a yellow oil in 19% yield by flash column
1
chromatography (hexane/ethyl acetate, 1:1) on silica gel. H NMR
1-(p-Methoxyphenyl)-5-(trifluoromethyl)pyrrolidin-2-one (9b): Com-
pound 9b (0.238 g) was obtained as a colorless solid in 92% yield
by flash column chromatography (hexane/ethyl acetate, 2:1) on sil-
(500 MHz, CDCl3): δ = 7.18 (t, J = 7.5 Hz, 1 H, ArH), 7.13 (t, J
= 7.5 Hz, 1 H, ArH), 6.78–6.74 (m, 2 H, ArH), 4.06–4.03 (m, 1 H,
CH), 3.69 (t, 2 H, OCH2), 2.23 (s, 3 H, CH3), 2.11–2.06 (m, 1 H,
1
ica gel. H NMR (500 MHz, CDCl3): δ = 7.21 (d, J = 9.0 Hz, 2 H,
CH2), 1.83–1.76 (m, 1 H, CH2), 1.76–1.67 (m, 2 H, CH2) ppm. 13
C
ArH), 6.93 (d, J = 9.0 Hz, 2 H, ArH), 4.52–4.46 (m, 1 H, CF3CH),
3.81 (s, 3 H, OCH3), 2.79–2.72 (m, 1 H, CH2), 2.58–2.43 (m, 2 H,
CH2), 2.33–2.28 (m, 1 H, CH2) ppm. 13C NMR (125 MHz,
CDCl3): δ = 174.8, 158.6, 129.8, 126.9, 125.3 (q, 1JC,F = 281.25 Hz),
1
NMR (125 MHz, CDCl3): δ = 144.5, 130.6, 127.4, 126.3 (q, JC,F
2
= 282.5 Hz), 122.9, 118.3, 110.8, 62.0, 55.4 (q, JC,F = 28.75 Hz),
28.4, 26.3, 17.5 ppm. 19F NMR (470 MHz, CDCl3): δ = –76.12 (d,
2
114.6, 61.5 (q, JC,F = 31.25 Hz), 55.5, 29.5, 19.5 ppm. 19F NMR
J = 4.7 Hz, CF ) ppm. IR (KBr): ν = 3428, 2928, 1606, 1519, 1481,
˜
3
1256, 1127, 748, 699 cm–1. C12H16F3NO (247.1): calcd. C 58.29, H
(470 MHz, CDCl3): δ = –75.09 (d, J = 4.7 Hz, CF3) ppm. IR (KBr):
ν = 3381, 2963, 1695, 1611, 1515, 1409, 837 cm–1. M.p. 128.6–
6.52, N 5.66; found C 58.03, H 6.41, N 5.44.
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130.1 °C. MS: m/z = 259.00. C12H12F3NO2 (259.0): calcd. C 55.60,
H 4.67, N 5.40; found C 55.87, H 4.51, N 5.21.
Methyl 5,5,5-Trifluoro-4-(p-fluorophenylamino)pentanoate (3f):
Compound 3f (0.374 g) was obtained as a pale-yellow oil in
67%yield by flash column chromatography (hexane/ethyl acetate,
4:1) on silica gel. H NMR (500 MHz, CDCl3): δ = 6.89 (t, 2 H, pound 9c (0.214 g) was obtained as a colorless solid in 88% yield
1-(p-Methylphenyl)-5-(trifluoromethyl)pyrrolidin-2-one (9c): Com-
1
ArH), 6.60–6.58 (m, 2 H, ArH), 3.96–3.89 (m, 1 H, CH), 3.65 (s,
3 H, OCH3), 3.60 (d, 1 H, NH), 2.57–2.45 (m, 2 H, CH2), 2.22–
by flash column chromatography (hexane/ethyl acetate, 2:1) on sil-
ica gel. 1H NMR (500 MHz, CDCl3): δ = 7.22–7.17 (m, 4 H, ArH),
2.16 (m, 1 H, CH2), 1.93–1.85 (m, 1 H, CH2) ppm. 13C NMR 4.58–4.52 (m, 1 H, CF3CH), 2.78–2.71 (m, 1 H, CH), 2.56–2.43
1
(125 MHz, CDCl3): δ = 173.4, 156.6 (d, JC,F = 235 Hz), 142.8 (d,
(m, 2 H, CH), 2.34 (s, 3 H, CH3), 2.30–2.238 (m, 1 H, CH) ppm.
4JC,F = 2.5 Hz), 126.1 (q, JC,F = 282 Hz), 115.9 (d, JC,F
=
13C NMR (125 MHz, CDCl3): δ = 174.8, 137.3, 134.6, 129.9, 127.7
1
2
3
2
1
2
22.5 Hz), 114.5 (d, JC,F = 7.5 Hz), 56.1 (q, JC,F = 29.2 Hz), 51.9,
(q, JC,F = 282.5 Hz), 125.2, 61.3 (q, JC,F = 31.25 Hz), 29.7, 21.1,
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Eur. J. Org. Chem. 2010, 1778–1786