The Journal of Organic Chemistry
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order. The chamber was sealed with a screwcap fitted with a Teflon
seal. The loaded two-chamber system was removed from the glovebox
and left at room temperature for 20 h. The title compound was
obtained after flash chromatography (10% EtOAc in pentane) as a
N-Benzyl-2-oxo-2-phenylacetamide (11).29 The same proce-
dure as for 5 using iodobenzene (102.0 mg, 0.50 mmol) and
benzylamine (110 μL, 1.00 mmol). The title compound was obtained
after flash chromatography (20% EtOAc in pentane) as a colorless
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solid (88.6 mg, 0.37 mmol, 74%). H NMR (400 MHz, CDCl3): δH
light yellow solid (94.0 mg, 0.36 mmol, 72%). H NMR (400 MHz,
ppm 8.37 (d, J = 7.2 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 8.0
Hz, 2H), 7.40−7.30 (m, 5H), 4.58 (d, J = 6.08 Hz, 2H). 13C NMR
(100 MHz, CDCl3): δC ppm 187.5, 161.5, 137.1, 134.4, 133.3, 131.2
(2C), 128.9 (2C), 128.5 (2C), 127.9 (2C), 127.8, 43.5. GCMS
C15H13O2N [M] Calcd: 239.09. Found: 239 (4%), 105 (100%), 91
(54%), 77 (46%).
CDCl3): δH ppm 8.42 (d, J = 8.3 Hz, 2H), 7.13 (bs, 1H), 6.94 (d, J =
9.1 Hz, 2H), 3.88 (s, 3H), 3.36 (q, J = 7.2 Hz, 2H), 1.59 (quin, J = 7.6
Hz, 2H), 1.40−1.31 (m, 6H), 0.89 (t, J = 6.5 Hz, 3H). 13C NMR (100
MHz, CDCl3): δC ppm 185.8, 164.6, 162.2, 133.9 (2C), 126.5, 113.8
(2C), 55.5, 39.4, 31.4, 29.3, 26.6, 22.5, 14.0. GCMS C15H21O3N [M]
Calcd: 263.15. Found: 263 (19%), 135 (100%), 92 (13%), 77 (16%).
2-(3,4-Dimethyoxyphenyl)-N-isopropyl-2-oxoactamide (6).
The same procedure as for 5 using 4-iodo-(1,2)-dimethoxybenzene
(132.0 mg, 0.50 mmol) and isopropylamine (82 μL, 1.0 mmol). The
title compound was obtained after flash chromatography (30% EtOAc
N-(tert-Butyl)-2-(2-methoxyphenyl)-2-oxoacetamide (12).30
The same procedure as for 5 using 2-iodoanisole (65 μL, 0.50
mmol) and tert-butylamine (106 μL, 1.00 mmol). The title compound
was obtained after flash chromatography (10% EtOAc in pentane) as a
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light yellow solid (102.3 mg, 0.44 mmol, 87%). H NMR (400 MHz,
in pentane) as a light yellow solid (103.0 mg, 0.41 mmol, 82%). H
CDCl3): δH ppm 7.63 (dd, J = 7.6 Hz, 1.7 Hz, 1H), 7.48 (td, J = 7.5
Hz, 5.0 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H),
6.46 (bs, 1H), 3.83 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz,
CDCl3): δC ppm 192.3, 162.4, 159.4, 134.3, 131.0, 124.7, 120.6, 111.9,
56.0, 51.5, 28.4 (3C). GCMS C13H17O3N [M] Calcd: 235.12. Found:
235 (6%), 135 (100%), 77 (13%).
NMR (400 MHz, CDCl3): δH ppm 8.25 (dd, J = 8.5 Hz, 1.9 Hz, 1H),
7.90 (d, J = 2.0 Hz, 1H), 6.97 (bs, 1H), 6.91 (d, J = 8.5 Hz, 1H), 4.14
(sep, J = 6.7 Hz, 1H), 3.96 (s, 3H), 3.94 (s, 3H), 1.26 (d, J = 6.6 Hz).
13C NMR (100 MHz, CDCl3): δC ppm 185.7, 161.4, 154.6, 148.7,
127.3, 126.5, 112.7, 110.2, 56.1, 56.0, 41.6, 22.4 (2C). HRMS
C13H17O4N [M + Na+] Calcd: 274.1055. Found: 274.1051. mp 100−
102 °C.
N-(tert-Butyl)-2-(2,4-dimethoxyphenyl)-2-oxoacetamide
(13). The same procedure as for 5 using 1-iodo-2,4-dimethoxybenzene
(132.0 mg, 0.50 mmol) and tert-butylamine (106 μL, 1.00 mmol). The
title compound was obtained after flash chromatography (30% EtOAc
N-(tert-Butyl)-2-(4-methoxyphenyl)-2-oxoacetamide (7).27
The same procedure as for 5 using 4-iodoanisole (117.0 mg, 0.50
mmol) and tert-butylamine (106 μL, 1.00 mmol). The title compound
was obtained after flash chromatography (10% EtOAc in pentane) as a
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in pentane) as a light yellow solid (100.5 mg, 0.38 mmol, 76%). H
NMR (400 MHz, CDCl3): δH ppm 7.74 (d, J = 8.6 Hz, 1H), 6.48 (dd,
J = 8.7 Hz, 2.3 Hz, 1H), 6.40 (d, J = 1.8 Hz, 1H), 6.38 (bs, 1H), 3.80
(s, 3H), 3.78 (s, 3H), 1.40 (s, 9H). 13C NMR (100 MHz, CDCl3): δC
ppm 190.0, 165.3, 163.7, 161.8, 133.7, 117.2, 105.5, 98.6, 55.8, 55.5,
51.4, 28.4 (3C). HRMS C14H19O4N [M + Na+] Calcd: 288.1206.
Found: 288.1209. mp 130−133 °C.
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light yellow solid (74.1 mg, 0.32 mmol, 63%). H NMR (400 MHz,
CDCl3): δH ppm 8.36 (d, J = 9.1 Hz, 2H), 6.97 (bs, 1H), 6.91 (d, J =
9.1 Hz, 2H), 3.85 (s, 3H), 1.43 (s, 9H). 13C NMR (100 MHz,
CDCl3): δC ppm 186.5, 164.5, 161.7, 133.9 (2C), 126.4, 113.7 (2C),
55.5, 51.5, 28.4 (3C). GCMS C13H17O3N [M] Calcd: 235.12. Found:
235 (13%), 135 (100%), 107 (16%), 92 (19%), 77 (20%).
N-(tert-Butyl)-2-(4-chlorophenyl)-2-oxoacetamide (14).29
The same procedure as for 5 using 1-chloro-4-iodobenzene (119.2
mg, 0.50 mmol) and tert-butylamine (106 μL, 1.00 mmol). The title
compound was obtained after flash chromatography (10% EtOAc in
pentane) as a light yellow solid (52.1 mg, 0.22 mmol, 44%). 1H NMR
(400 MHz, CDCl3): δH ppm 8.28 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.5
Hz, 2H), 6.96 (bs, 1H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3):
δC ppm 187.1, 160.7, 140.9, 132.7 (2C), 131.7, 128.7 (2C), 51.7, 28.3
(3C). GCMS C12H14O2NCl [M] Calcd: 239.07. Found: 239 (13%),
139 (100%), 111 (25%), 57 (28%).
N-(tert-Butyl)-2-(3,4-dimethoxyphenyl)-2-oxoacetamide (8).
The same procedure as for 5 using 4-iodo-(1,2)-dimethoxybenzene
(132.0 mg, 0.50 mmol) and tert-butylamine (106 μL, 1.00 mmol). The
title compound was obtained after flash chromatography (20% EtOAc
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in pentane) as a light yellow solid (120.6 mg, 0.45 mmol, 91%). H
NMR (400 MHz, CDCl3): δH ppm 8.22 (dd, J = 8.5 Hz, 2.0 Hz, 1H),
7.86 (d, J = 2.0 Hz, 1H), 6.97 (bs, 1H), 6.90 (d, J = 8.6 Hz, 1H), 3.96
(s, 3H), 3.94 (s, 3H), 1.45 (s, 9H). 13C NMR (100 MHz, CDCl3): δC
ppm 186.4, 161.7, 154.5, 148.7, 127.3, 126.4, 112.7, 110.1, 107.9, 56.1,
56.0, 51.5, 28.4 (3C). HRMS C14H19O4N [M + K+] Calcd: 304.0946.
Found: 304.0948.
N-Benzyl-2-(3,4-dimethoxyphenyl)-2-oxoacetamide (9). The
same procedure as for 5 using 4-iodo-(1,2)-dimethoxybenzene (132.0
mg, 0.50 mmol) and benzylamine (110 μL, 1.00 mmol). The title
compound was obtained after flash chromatography (20% EtOAc in
pentane) as a light yellow solid (140.6 mg, 0.47 mmol, 94%). 1H NMR
(400 MHz, CDCl3): δH ppm 8.29 (d, J = 8.5 Hz, 1H), 7.89 (s, 1H),
7.46 (bs, 1H), 7.38−7.30 (m, 4H), 6.92 (d, J = 8.6 Hz, 1H), 4.56 (d, J
= 6.0 Hz, 2H), 3.97 (s, 3H), 3.94 (s, 3H). 13C NMR (100 MHz,
CDCl3): δC ppm 185.2, 162.0, 154.7, 148.8, 137.2, 128.8 (2C), 127.8
(2C), 127.7, 127.4, 126.4, 112.7, 110.2, 56.1, 56.0, 43.4. HRMS
C17H17O4N [M + Na+] Calcd: 322.1050. Found: 322.1053. mp 82−84
°C.
N-(tert-Butyl)-2-oxo-2-(o-tolyl)acetamide (15).29 The same
procedure as for 5 using 2-iodotoluene (109.0 mg, 0.50 mmol) and
tert-butylamine (106 μL, 1.00 mmol). The title compound was
obtained after flash chromatography (10% EtOAc in pentane) as a
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light yellow solid (93.7 mg, 0.43 mmol, 85%). H NMR (400 MHz,
CDCl3): δH ppm 8.36 (d, J = 8.0 Hz, 1H), 7.40 (td, J = 7.5 Hz, 1.4 Hz,
1H), 7.27−7.23 (m, 2H), 6.92 (bs, 1H), 2.46 (s, 3H), 1.44 (s, 9H).
13C NMR (100 MHz, CDCl3): δC ppm 192.3, 161.3, 139.7, 133.0,
132.4, 131.7, 125.2, 51.6, 28.3 (3C), 20.7. GCMS C13H17O2N [M]
Calcd: 219.13. Found: 219 (19%), 119 (100%), 91 (38%), 57 (22%).
Ethyl 4-(2-Oxo-2-(pyrrolidin-1-yl)acetyl)benzoate (16).15f
The same procedure as for 5 using ethyl 4-iodobenzoate. Flash
column chromatography using 30% diethyl ether in pentane as eluent
resulted in 92.5 mg (67% yield) of the title product as a yellow solid.
1H NMR (400 MHz, CDCl3): δH ppm 8.11 (d, J = 8.4 Hz, 2H), 8.02
(d, J = 8.2 Hz, 2H), 4.37 (q, J = 7.2 Hz, 2H), 3.62 (t, J = 7.0 Hz, 2H),
3.40 (t, J = 6.6 Hz, 2H), 1.93−1.91 (m, 4H), 1.37 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δC ppm 190.6, 165.4, 164.1, 136.1,
135.4, 129.9 (2 C), 129.7 (2 C), 61.5, 46.7, 45.4, 25.9, 23.9, 14.2.
HRMS C15H17NO4 [M + Na+] Calcd: 298.1055. Found: 298.1055.
N-(tert-Butyl)-2-oxo-2-(thiophen-2-yl)acetamide (17). The
same procedure as for 5 using 2-iodothiophene (105.0 mg, 0.50
mmol) and tert-butylamine (106 μL, 1.00 mmol). The title compound
was obtained after flash chromatography (2% ethyl acetate in pentane
→ 5% ethyl acetate in pentane) as a light yellow solid (80.3 mg, 0.38
2-(3,4-Dimethoxyphenyl)-N-(4-methoxybenzyl)-2-oxoaceta-
mide (10). The same procedure as for 5 using 4-iodo-(1,2)-
dimethoxybenzene (132.0 mg, 0.50 mmol) and (4-methoxyphenyl)-
methanamine (131 μL, 1.00 mmol). The title compound was obtained
after flash chromatography (30% EtOAc in pentane) as a light yellow
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solid (153.8 mg, 0.47 mmol, 93%). H NMR (400 MHz, CDCl3): δH
ppm 8.25 (dd, J = 8.5 Hz, 1.9 Hz, 1H), 7.88 (d, J = 1.8 Hz, 1H), 7.41
(bs, 1H), 7.24 (s, 1H), 6.92−6.86 (m, 3H), 4.48 (d, J = 10.0 Hz, 2H),
3.96 (s, 3H), 3.93 (s, 3H), 3.79 (s, 3H). 13C NMR (100 MHz,
CDCl3): δC ppm 185.4, 162.0, 159.2, 154.7, 148.8, 129.2 (2C), 127.4,
126.4, 114.7 (2C), 112.6, 110.2, 56.1, 56.0, 55.3, 42.9. HRMS
C18H19O5N [M + Na+] Calcd: 352.1161. Found: 352.1155. mp 128−
130 °C.
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mmol, 76%). H NMR (400 MHz, CDCl3): δH ppm 8.33 (d, J = 5.1
Hz, 1H), 7.78 (d, J = 6.1 Hz, 1H), 7.18 (bs, 1H), 7.14 (t, J = 4.0 Hz,
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dx.doi.org/10.1021/jo3009337 | J. Org. Chem. 2012, 77, 6155−6165