Page 7 of 10
The Journal of Organic Chemistry
124.1 (q, J = 270.3 Hz), 79.8, 56.3, 33.3, 28.4. 19F NMR (376
(100 MHz, CDCl3, ppm) δ = 158.3, 156.5, 137.2, 131.7, 126.4,
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116.1, 111.1, 79.4, 55.2, 30.1, 28.4, 28.4, 19.7. HRMS (ESI-
TOF) m/z: [M+Na]+ Calcd for C16H23NO3Na 300.1570; found
300.1575.
MHz, CDCl3, ppm) δ = - 62.5. MS (ESI, m/z): [M+Na]+ 324.2.
tert-butyl 3-(3-(trifluoromethyl)phenyl)azetidine-1-carboxylate
(3an).17 Colorless oil (98 mg, yield 65%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.53 - 7.45 (m, 4 H), 4.36 (t, J = 8.7 Hz, 2 H), 3.98 -
3.95 (m, 2 H), 3.82 - 3.74 (m, 1 H), 1.47 (s, 9 H). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ = 156.4, 143.2, 131.1 (q, J =
40.0 Hz), 130.1, 129.3, 124.0 (q, J = 270.7 Hz), 123.9 (q, J =
3.7 Hz), 123.7 (q, J = 3.7 Hz), 79.8, 56.3, 33.3, 28.4. 19F NMR
(376 MHz, CDCl3, ppm) δ = - 62.6. MS (ESI, m/z): [M+K]+
340.0.
tert-butyl 3-(4-(tert-butyl)phenyl)azetidine-1-carboxylate (3af).
Colorless oil (117 mg, yield 81%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.41 - 7.39 (m, 2 H), 7.28 - 7.26 (m, 2 H), 4.33 (t, J
= 8.6 Hz, 2 H), 4.02 - 3.94 (m, 2 H), 3.78 - 3.70 (m, 1 H), 1.49
(s, 9 H), 1.35 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3, ppm)
δ = 156.5, 149.9, 139.2, 126.5, 125.6, 79.4, 56.8, 34.5, 33.1,
31.3, 28.4. MS (ESI, m/z): [M+Na]+ 312.1.
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tert-butyl 3-(4-methoxyphenyl)azetidine-1-carboxylate (3ag).7g
Colorless oil (101 mg, yield 77%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.23 - 7.20 (m, 2 H), 6.89 - 6.85 (m, 2 H), 4.29 (t, J
= 8.7 Hz, 2 H), 3.94-3.90 (m, 2 H), 3.78 (s, 3 H), 3.74 - 3.60
(m, 1 H), 1.46 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ = 158.6, 156.4, 134.3, 127.8, 114.1, 79.4, 56.8, 55.3,
32.9, 28.4. MS (ESI, m/z): [M+Na]+ 286.1.
tert-butyl 3-(4-fluorophenyl)azetidine-1-carboxylate (3ao).6b
Colorless oil (88 mg, yield 70%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.21 - 7.17 (m, 2 H), 6.98 - 6.92 (m, 2 H), 4.24 (t, J
= 8.8 Hz, 2 H), 3.87-3.83 (m, 2 H), 3.66 - 3.59 (m, 1 H), 1.39
(s, 9 H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ = 163.0 (d,
J = 243.9 Hz), 156.4, 138.0 (d, J = 3.3 Hz), 128.3 (d, J = 8.0
Hz), 115.6 (d, J = 21.3 Hz), 79.6, 56.7, 32.9, 28.4. 19F NMR
(376 MHz, CDCl3, ppm) δ = - 115.7. MS (ESI, m/z): [M+Na]+
274.1
tert-butyl 3-(3-methoxyphenyl)azetidine-1-carboxylate (3ah).6f
Colorless oil (85 mg, yield 65%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.27 - 7.23 (m, 1 H), 6.89 - 6.77 (m, 3 H), 4.30 (t, J
= 8.7 Hz, 2 H), 3.98-3.95 (m, 2 H), 3.80 (s, 3 H), 3.73 - 3.66
(m, 1 H), 1.46 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ = 159.9, 156.4, 143.9, 129.7, 119.0, 112.6, 112.2, 79.5,
56.5, 55.2 (d, J = 2.2 Hz), 33.5, 28.4. MS (ESI, m/z): [M+Na]+
286.1.
tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate (3ai).
Colorless oil (37 mg, yield 30%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.11 - 7.09 (m, 2 H), 6.68 - 6.66 (m, 2 H), 4.27 (t, J
= 8.6 Hz, 2 H), 3.93-3.89 (m, 2 H), 3.66-3.59 (m, 3 H), 1.46 (s,
9 H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ = 156.5,
145.3, 132.2, 127.7, 115.3, 79.4, 56.8, 32.9, 28.4. MS (ESI,
m/z): [M+Na]+ 271.9.
tert-butyl 3-(3-fluorophenyl)azetidine-1-carboxylate (3ap).17
Colorless oil (82 mg, yield 65%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.25 - 7.19 (m, 1 H), 7.00 - 6.99 (m, 1 H), 6.96 -
6.92 (m, 1 H), 6.89 - 6.84 (m, 1 H), 4.25 (t, J = 8.8 Hz, 2 H),
3.88 - 3.83 (m, 2 H), 3.67 - 3.60 (m, 1 H), 1.39 (s, 9 H).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ = 163.3 (d, J =
244.8 Hz), 155.3, 143.9 (d, J = 7.0 Hz), 129.3 (d, J = 8.2 Hz),
121.4 (d, J = 2.8 Hz), 113.0 (d, J = 15.1 Hz), 112.8 (d, J =
15.8 Hz), 78.6, 55.4, 32.3, 27.4. 19F NMR (376 MHz, CDCl3,
ppm) δ = - 112.7. MS (ESI, m/z): [M+Na]+ 274.3.
tert-butyl 3-(4-chlorophenyl)azetidine-1-carboxylate (3aq).6f
Colorless oil (96 mg, yield 72%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.31 - 7.28 (m, 2 H), 7.24 - 7.22 (m, 2 H), 4.33-4.29
(m, 2 H), 3.94-3.89 (m, 2 H), 3.71 - 3.64 (m, 1 H), 1.45 (s, 9
H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ = 156.3, 140.8,
132.7, 128.8, 128.1, 79.6, 56.6, 33.0, 28.4. MS (ESI, m/z):
[M+Na]+ 290.1.
tert-butyl
3-(4-(trifluoromethoxy)phenyl)azetidine-1-
carboxylate (3ak).17 Colorless oil (114 mg, yield 72%),
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purified by flash chromatography (PE:EA = 10:1). H NMR
(400 MHz, CDCl3, ppm): δ = 7.35 - 7.31 (m, 2 H), 7.20 - 7.18
(m, 2 H), 4.33 (t, J = 8.7 Hz, 2 H), 3.96 - 3.91 (m, 2 H), 3.76 -
3.69 (m, 1 H), 1.46 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ = 156.4, 148.1 (d, J = 1.6 Hz), 141.0, 128.1, 121.3,
120.5 (q, J = 255.4 Hz), 79.7, 56.5, 32.9, 28.4. 19F NMR (376
MHz, CDCl3, ppm) δ = - 57.9. MS (ESI, m/z): [M+Na]+ 340.2.
tert-butyl 3-(3-chlorophenyl)azetidine-1-carboxylate (3ar).17
Colorless oil (83 mg, yield 62%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3,
ppm): δ = 7.23 - 7.11 (m, 4 H), 4.25 (t, J = 8.7 Hz, 2 H), 3.89-
3.84 (m, 2 H), 3.66 - 3.58 (m, 1 H), 1.39 (s, 9 H). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ = 156.3, 144.3, 134.6, 130.0,
127.2, 127.0, 124.9, 79.7, 56.4, 33.2, 28.4. MS (ESI, m/z):
[M+Na]+ 290.0.
tert-butyl
3-(3-(trifluoromethoxy)phenyl)azetidine-1-
carboxylate (3al).17 Colorless oil (101 mg, yield 64%),
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purified by flash chromatography (PE:EA = 10:1). H NMR
(400 MHz, CDCl3): δ = 7.32 - 7.28 (m, 1 H), 7.19 - 7.17 (m, 1
H), 7.07 - 7.03 (m, 2 H), 4.27 (t, J = 8.8 Hz, 2 H), 3.90 - 3.86
(m, 2 H), 3.70 - 3.63 (m, 1 H), 1.39 (s, 9 H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 156.3, 149.6 (d, J = 1.6 Hz), 144.6,
130.1, 125.1, 120.4 (q, J = 255.6 Hz), 119.5, 119.4, 79.6, 56.2,
33.2, 28.4. 19F NMR (376 MHz, CDCl3, ppm) δ = - 57.8. MS
(ESI, m/z): [M+Na]+ 340.1.
tert-butyl 3-(4-(trifluoromethyl)phenyl)azetidine-1-carboxylate
(3am).17 Colorless oil (105 mg, yield 70%), purified by flash
chromatography (PE:EA = 10:1). 1H NMR (400 MHz, CDCl3):
δ = 7.60 (d, J = 8.2 Hz, 2 H), 7.43 (d, J = 8.2 Hz, 2 H), 4.35 (t,
J = 8.7 Hz, 2 H), 3.98 - 3.92 (m, 2 H), 3.81 - 3.73 (m, 1 H),
1.46 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3): δ = 156.3,
146.3, 129.3 (q, J = 32.3 Hz), 127.1, 125.7 (q, J = 3.7 Hz),
tert-butyl 3-([1,1'-biphenyl]-4-yl)azetidine-1-carboxylate (3at).
White solid (99 mg, yield 64%), purified by flash
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chromatography (PE:EA = 10:1). m.p. 89-91 °C . H NMR
(400 MHz, CDCl3, ppm): δ = 7.61 - 7.59 (m, 4 H), 7.47 - 7.43
(m, 2 H), 7.41 - 7.34 (m, 3 H), 4.37 (t, J = 8.7 Hz, 2 H), 4.05 -
4.01 (m, 2 H), 3.82 - 3.75 (m, 1 H), 1.50 (s, 9 H). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ = 155.4, 140.3, 139.7, 138.9,
127.8, 126.4, 126.3, 126.2, 126.0, 78.5, 55.5, 32.2, 27.4. MS
(ESI, m/z): [M+K]+ 348.1.
tert-butyl
3-(benzo[b]thiophen-5-yl)azetidine-1-carboxylate
(3au). White solid (69 mg, yield 48 %), purified by flash
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chromatography (PE:EA = 10:1). m.p. 96-98 °C . H NMR
(400 MHz, CDCl3, ppm): δ = 7.85 - 7.83 (m, 1 H), 7.74 - 7.73
(m, 1 H), 7.45 - 7.44 (m, 1 H), 7.31 - 7.29 (m, 2 H), 4.38 (t, J
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