S. Pichette, S. Aubert-Nicol, J. Lessard, C. Spino
FULL PAPER
tion was carried out on a 1.27 mmol scale, the reaction time was
4.25 h, the solution was stirred at room temperature for 15 min, the
eluent for the flash chromatography was a mixture of ethyl acetate
and hexanes (10:90 and 40:60), and the product was obtained in
56% yield as a colourless oil. 1H NMR (400 MHz, CDCl3): δ =
3.64 (s, 3 H), 3.51–3.44 (m, 1 H), 3.42–3.24 (m, 2 H), 1.70 (ddd, J
= 10.9, 10.9, 10.9 Hz, 1 H), 1.50 (dt, J = 10.9, 5.5 Hz, 1 H), 1.09–
088 (m, 3 H), 0.96 (s, 3 H), 0.94 (s, 3 H) ppm. 13C NMR
(100.7 MHz, CDCl3): Rotamer A: δ = 156.1 (s), 62.7 (d), 52.3 (q),
44.6 (t), 40.9 (s), 36.9 (t), 27.7 (q), 23.2 (q), 16.8 (q) ppm; Rot-
amer B: δ = 155.8 (s), 62.3 (d), 52.2 (q), 44.3 (t), 40.1 (s), 35.9 (t),
(3) [M – CH3]+, 156 (20) [M – OMe]+, 124 (15), 113 (60), 74 (100).
HRMS: calcd. for C9H16NO3 [M – H]+ 186.1130; found 186.1133.
Methyl 5-(4-Methoxyphenyl)-2,2-dimethylpyrrolidine-1-carboxylate
(32): Carbamate 32 was synthesized according to the general pro-
cedure. The reaction was carried out on a 0.92 mmol scale, the
reaction time was 30 min, the solution was stirred at room tempera-
ture for 15 min, the eluent for the flash chromatography was a mix-
ture of ethyl acetate and hexanes (10:90 and 20:80), and the product
was obtained in 47% yield as a colourless oil. 1H NMR (300 MHz,
CDCl3): Rotamer A: δ = 7.20–7.03 (m, 2 H), 6.84 (d, J = 8.7 Hz,
2 H), 5.06–4.91 (m, 1 H), 3.79 (s, 3 H), 3.48 (s, 3 H), 2.40–2.20 (m,
2 H), 2.02–1.53 (m, 2 H), 1.67 (s, 3 H), 1.43 (s, 3 H) ppm; Rot-
amer B: δ = 7.20–7.03 (m, 2 H), 6.84 (d, J = 8.7 Hz, 2 H), 5.06–
4.91 (m, 1 H), 3.69 (s, 3 H), 3.48 (s, 3 H), 2.40–2.20 (m, 2 H), 2.02–
1.53 (m, 2 H), 1.58 (s, 3 H), 1.37 (s, 3 H) ppm. 13C NMR
27.5 (q), 23.0 (q), 16.0 (q) ppm. IR (CHCl ): ν = 2960, 2875, 1689,
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1456, 1382, 1340, 1294, 1122, 1051 cm–1. MS: m/z (%) = 171 (15)
[M]+, 156 (100), 115 (80), 97 (15). HRMS: calcd. for C9H17NO2
[M]+ 171.1259; found 171.1264.
1-(1-Methoxyethyl)-5,5-dimethylpyrrolidin-2-one (27): Lactam 27 (100.7 MHz, CDCl3): Rotamer A: δ = 158.3 (s), 155.1 (s), 136.8 (s),
was synthesized according to the general procedure. The reaction
was carried out on a 1.27 mmol scale, the reaction time was 4.25 h,
the solution was stirred at room temperature for 15 min, the eluent
for the flash chromatography was a mixture of ethyl acetate and
hexanes (10:90 and 40:60), and the product was obtained in 10%
126.6 (d), 113.7 (d), 63.5 (s), 62.5 (d), 55.5 (q), 51.9 (q), 38.9 (t),
32.3 (t), 27.3 (q), 25.2 (q) ppm; Rotamer B: δ = 158.3 (s), 156.1 (s),
136.4 (s), 126.8 (d), 113.8 (d), 63.5 (s), 62.1 (d), 55.5 (q), 52.1 (q),
40.2 (t), 31.7 (t), 28.2 (q), 26.5 (q) ppm. IR (CHCl ): ν = 3051,
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2995, 2935, 1689, 1615, 1587, 1446, 1372, 1298, 1174, 1086 cm–1.
yield as a colourless oil. 1H NMR (300 MHz, CDCl3): δ = 5.33 (q, MS: m/z (%) = 263 (60) [M]+, 248 (90) [M – Me]+, 207 (100), 173
J = 6.4 Hz, 1 H), 3.25 (s, 3 H), 2.42 (t, J = 8.8 Hz, 1 H), 2.41 (t, J
= 6.8 Hz, 1 H), 1.82 (t, J = 8.2 Hz, 2 H), 1.50 (d, J = 6.4 Hz, 3 H),
1.40 (s, 3 H), 1.37 (s, 3 H) ppm. 13C NMR (100.7 MHz, CDCl3): δ
= 175.9 (s), 81.1 (d), 61.7 (s), 55.8 (q), 36.3 (t), 30.2 (t), 28.5 (q),
(75). HRMS: calcd. for C15H21NO3 [M]+ 263.1521; found
263.1523.
6-(4-Methoxyphenyl)-3,3-dimethyl-3,4-dihydropyridin-2(1H)-one (36)
and 1-[Methoxy(4-methoxyphenyl)methyl]-3,3-dimethylpyrrolidin-2-
one (33): Lactams 36 and 33 were synthesized according to the
general procedure. The reaction was carried out on a 0.92 mmol
scale, the reaction time was 30 min, the solution was stirred at room
temperature for 15 min, the eluent for the flash chromatography
was a mixture of ethyl acetate and hexanes (10:90 and 20:80), and
a mixture of the products (2:1) was obtained in 43% yield as a
28.2 (q), 20.8 (q) ppm. IR (CHCl ): ν = 2992, 2942, 2826, 1664,
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1449, 1403, 1354, 1245, 1189, 1139, 1093, 1051, 910, 847 cm–1. MS:
m/z (%) = 171 (10) [M]+, 156 (100), 115 (60), 98 (35), 84 (20).
HRMS: calcd. for C9H17NO2 [M]+ 171.1259; found 171.1264.
Methyl 5-Methoxy-2,2-dimethylpyrrolidine-1-carboxylate (29) and
Methyl 5,5-Dimethoxy-2-methylpent-2-ylcarbamate (34): Carb-
amates 29 and 34 were synthesized according to the general pro-
cedure. The reaction was carried out on a 0.31 mmol scale, the
reaction time was 1 h, the solution was stirred at room temperature
for 15 min, the solvent was removed under reduced pressure and
the crude mixture was directly purified by flash chromatography.
The eluent was a mixture of ethyl acetate and hexanes (15:85), and
the products were obtained in 17% yield for 29 (not characterized
1
beige solid. Lactam 36: H NMR (300 MHz, CDCl3): δ = 7.33 (d,
J = 8.6 Hz, 2 H), 7.11 (s, 1 H), 6.89 (d, J = 8.6 Hz, 2 H), 5.27 (td,
J = 4.7, 1.6 Hz, 1 H), 3.81 (s, 3 H), 2.30 (d, J = 4.7 Hz, 2 H), 1.21
(s, 6 H) ppm. 13C NMR (100.7 MHz, CDCl3): δ = 177.4 (s), 160.1
(s), 136.1 (s), 127.8 (s), 127.4 (d), 114.4 (d), 100.4 (d), 55.6 (q), 37.1
(s), 36.1 (t), 24.7 (q) ppm. IR (CHCl ): ν = 3544–3023 (br.), 2995,
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2967, 2939, 2872, 2844, 1689, 1657, 1611, 1460, 1446, 1287, 1178,
because of instability) and in 29% yield for 34 as colourless oils.
1079 cm–1. MS: m/z (%) = 231 (90) [M]+, 216 (100), 203 (35), 188
1
Carbamate 34: H NMR (400 MHz, CDCl3): δ = 4.65 (br. s, 1 H), (65), 162 (35), 146 (40), 134 (50). HRMS: calcd. for C14H17NO
4.34 (t, J = 5.5 Hz, 1 H), 3.59 (br. s, 3 H), 3.31 (s, 6 H), 1.75–1.64 [M]+ 231.1259; found 231.1263. Lactam 33: H NMR (300 MHz,
1
(m, 2 H), 1.63–1.53 (m, 2 H), 1.27 (s, 6 H) ppm. 13C NMR CDCl3): δ = 7.26 (d, J = 8.2 Hz, 2 H), 6.86 (d, J = 8.2 Hz, 2 H),
(100 MHz, CDCl3): δ = 155.5 (s), 104.9 (d), 53.0 (q), 52.5 (s), 51.7 6.19 (s, 1 H), 3.79 (s, 3 H), 3.40 (s, 3 H), 3.23–3.11 (m, 1 H), 2.87–
(q), 35.3 (t), 29.9 (t), 27.6 (t), 27.3 (q) ppm. IR (CHCl ): ν = 3411–
2.74 (m, 1 H), 1.91–1.66 (m, 2 H), 1.23 (s, 3 H), 1.14 (s, 3 H) ppm.
13C NMR (100.7 MHz, CDCl3): δ = 181.1 (s), 159.5 (s), 129.9 (s),
126.2 (d), 113.9 (d), 82.6 (d), 55.9 (q), 55.5 (q), 41.7 (s), 38.0 (t),
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3137 (br.), 3017, 2960, 2837, 1720, 1509, 1269, 1206, 1121,
1058 cm–1. MS: m/z (%) = 204 (2) [M – CH3]+, 188 (10) [M –
OMe]+, 172 (25), 156 (40), 116 (100), 97 (15). HRMS: calcd. for 34.2 (t), 24.9 (q), 24.5 (q) ppm. IR (CHCl ): ν = 3544–3023 (br.),
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C9H18NO4 [M – CH3]+ 204.1236; found 204.1239.
2995, 2967, 2939, 2872, 2844, 1689, 1657, 1611, 1460, 1446, 1287,
1178, 1079 cm–1. MS: m/z (%) = 263 (5) [M]+, 248 (50) [M –
Me]+, 232 (20), 135 (100). HRMS: calcd. for C15H21NO3 [M]+
263.1521; found 263.1526.
4-Isocyanato-1,1-dimethoxy-4-methylpentane (35): Isocyanate 35
was synthesized according to the general procedure. The reaction
was carried out on a 0.58 mmol scale, the reaction time was 30 min,
the solution was stirred at room temperature for 18 h, the solvent
was removed under reduced pressure, the crude product was di-
rectly purified by flash chromatography, the eluent was a mixture
of ethyl acetate and hexanes (15:85), and the product was obtained
cis-4a-Methyloctahydroquinoline-2(1H)-thione (38): Thiolactam 38
was synthesized according to the general procedure. The reaction
was carried out on a 0.49 mmol scale, the reaction time was 30 min,
the solution was stirred at room temperature for 15 min, the solvent
was removed under reduced pressure, the crude mixture was di-
rectly purified by flash chromatography, the eluent was a mixture
1
in 17% yield as a colourless oil. H NMR (400 MHz, CDCl3): δ =
4.36 (t, J = 5.4 Hz, 2 H), 3.32 (s, 6 H), 1.76–1.60 (m, 2 H), 1.59–
1.51 (m, 2 H), 1.34 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ of ethyl acetate and hexanes (5:95), and the product was obtained
1
= 122.6 (s), 104.5 (d), 58.1 (s), 53.1 (q), 38.6 (t), 30.4 (q), 28.0 (t)
in 30% yield as a colourless oil. H NMR (300 MHz, CDCl3): δ =
ppm. IR (CHCl ): ν = 3013, 2982, 2939, 2837, 2259, 1463, 1445, 8.64 (br. s, 1 H), 3.16–3.08 (m, 1 H), 2.93 (t, J = 6.6 Hz, 2 H),
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1386, 1364, 1125, 1072 cm–1. MS: m/z (%) = 186 (3) [M – H]+, 172
1.90–1.79 (m, 1 H), 1.72 (dt, J = 13.6, 6.6 Hz, 1 H), 1.62–1.32 (m,
1334
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Eur. J. Org. Chem. 2012, 1328–1335