Organic Process Research & Development
Article
4-(Phenylsulfonyl)morpholine (2a).27 204 mg (90%) as a
white solid (mp 118−120 °C, lit. 118−120 °C); H NMR
Methyl (Phenylsulfonyl)-L-phenylalaninate (2j).32 198 mg
(62%) as a white solid (mp 100−102 °C, lit. 100−103 °C); 1H
NMR (400 MHz, CDCl3): δ 7.80−7.67 (m, 2H), 7.59−7.49
(m, 1H), 7.49−7.38 (m, 2H), 7.31−7.18 (m, 3H), 7.11−7.01
(m, 2H), 5.13 (d, J = 9.3 Hz, 1H), 4.22 (dt, J = 9.3, 6.0 Hz,
1H), 3.47 (s, 3H), 3.04 (dd, J = 6.0, 1.7 Hz, 2H), 1.65 (s, 1H);
13C NMR (100 MHz, CDCl3): δ 171.1, 139.4, 134.8, 132.8,
129.3, 129.0, 128.6, 127.3, 127.1, 56.6, 52.4, 39.3; MS (ESI)
m/z: 320.37 (M + H)+.
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(400 MHz, CDCl3): δ 7.71 (dd, J = 8.9, 5.1 Hz, 2H), 7.23−
7.09 (m, 3H), 3.72−3.60 (m, 4H), 2.99−2.85 (m, 4H); 13C
NMR (101 MHz, CDCl3): δ 135.0, 133.0, 129.1, 127.7, 66.0,
45.9; MS (ESI) m/z: 228.08 (M + H)+.
1-(Phenylsulfonyl)piperidine (2b).3 213 mg (95%) as a
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white solid (mp 92−94 °C, lit. 91−93 °C); H NMR (400
MHz, CDCl3): δ 7.79−7.73 (m, 2H), 7.61−7.48 (m, 3H),
3.04−2.94 (m, 4H), 1.64 (ddd, J = 11.4, 5.9, 4.1 Hz, 4H),
1.48−1.36 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 136.4,
132.5, 128.9, 127.6, 46.9, 25.2, 23.5; MS (ESI) m/z: 226.32
(M + H)+.
N-Methylbenzenesulfonamide (2k).33 154 mg (90%) as a
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white solid (mp 43−46 °C, lit. 44−45 °C); H NMR (400
MHz, CDCl3): δ 7.91−7.81 (m, 2H), 7.62−7.55 (m, 1H),
7.55−7.48 (m, 2H), 4.86 (d, J = 5.5 Hz, 1H), 2.64 (d, J = 5.4
Hz, 4H); 13C NMR (100 MHz, CDCl3): δ 138.5, 132.7, 129.1,
127.1, 29.3; MS (ESI) m/z: 172.22 (M + H)+.
1-(Phenylsulfonyl)pyrrolidine (2c).28 198 mg (94%) as a
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white solid (mp 92−93 °C, lit. 91−93 °C); H NMR (400
Benzenesulfonamide (2l).33 128 mg (82%) as a white solid
MHz, CDCl3): δ 7.85−7.75 (m, 2H), 7.62−7.45 (m, 3H),
3.29−3.17 (m, 4H), 1.81−1.64 (m, 4H); 13C NMR (100
MHz, CDCl3): δ 136.6, 132.5, 128.9, 127.4, 47.9, 25.1; MS
(ESI) m/z: 212.28 (M + H)+.
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(mp 143−145 °C, lit. 139−142 °C); H NMR (400 MHz,
methanol-d4): δ 7.97−7.84 (m, 2H), 7.64−7.41 (m, 3H); 13C
NMR (100 MHz, methanol-d4): δ 145.2, 133.3, 130.2, 130.1,
127.2, 127.2; MS (ESI) m/z: 158.18 (M + H)+.
tert-Butyl 4-(phenylsulfonyl)piperazine-1-carboxylate
(2d).29 273 mg (84%) as a white solid (mp 126−128 °C, lit.
127−128 °C); 1H NMR (400 MHz, CDCl3): δ 7.76−7.71 (m,
2H), 7.64−7.58 (m, 1H), 7.56−7.50 (m, 2H), 3.55−3.43 (m,
4H), 2.95 (t, J = 5.1 Hz, 4H), 1.38 (s, 9H); 13C NMR (100
MHz, CDCl3): δ 154.1, 135.2, 133.0, 129.1, 127.6, 80.3, 45.8,
28.2; MS (ESI) m/z: 327.41 (M + H)+.
1-(Phenylsulfonyl)-1H-benzo[d]imidazole (2m).30 209 mg
(81%) as a white solid (mp 104−106 °C, lit. 105−106 °C); 1H
NMR (400 MHz, CDCl3): δ 7.76−7.71 (m, 2H), 7.64−7.58
(m, 1H), 7.56−7.50 (m, 2H), 3.55−3.43 (m, 4H), 2.95 (t, J =
5.1 Hz, 4H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3): δ
154.1, 135.2, 133.0, 129.1, 127.6, 80.3, 45.8, 28.2; MS (ESI)
m/z: 259.18 (M + H)+.
N-Cyclopropylbenzenesulfonamide (2e).29 147 mg (75%)
as a white solid (mp 52−54 °C, lit. 53−55 °C); 1H NMR (400
MHz, CDCl3): δ 7.96−7.83 (m, 2H), 7.66−7.47 (m, 3H), 4.98
(s, 1H), 2.24 (tddd, J = 7.1, 4.2, 3.5, 1.3 Hz, 1H), 0.60 (ddt, J =
8.2, 4.0, 2.3 Hz, 4H); 13C NMR (100 MHz, CDCl3): δ 139.5,
132.8, 129.1, 127.4, 24.3, 6.2; MS (ESI) m/z: 198.22 (M +
H)+.
4-((3-Methoxyphenyl)sulfonyl)morpholine (2n).19 246 mg
(96%) as a white solid (mp 128−130 °C, lit. 128−129 °C); 1H
NMR (400 MHz, CDCl3): δ 7.44 (t, J = 8.0 Hz, 1H), 7.32−
7.29 (m, 1H), 7.22 (dd, J = 2.6, 1.6 Hz, 1H), 7.15−7.08 (m,
1H), 3.84 (s, 3H), 3.77−3.65 (m, 4H), 2.99 (dd, J = 5.7, 3.9
Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 159.8, 135.9, 130.1,
119.8, 119.0, 112.6, 66.0, 55.6, 45.9; MS (ESI) m/z: 258.30
(M + H)+.
N-Hexylbenzenesulfonamide (2f).30 204 mg (85%) as
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yellow oil; H NMR (400 MHz, CDCl3): δ 7.92−7.80 (m,
4-((4-Fluorophenyl)sulfonyl)morpholine (2o).15c 191 mg
(78%) as a white solid (mp 101−105 °C, lit. 103−105 °C); 1H
NMR (400 MHz, CDCl3): δ 7.77 (dd, J = 8.9, 5.1 Hz, 2H),
7.28−7.14 (m, 2H), 3.79−3.57 (m, 4H), 3.04−2.93 (m, 4H);
13C NMR (100 MHz, CDCl3): δ 166.6, 164.1, 131.0, 131.0,
130.5, 130.4, 116.6, 116.3, 66.0, 45.9; MS (ESI) m/z: 246.26
(M + H)+.
2H), 7.63−7.44 (m, 3H), 4.72 (t, J = 6.2 Hz, 1H), 2.94 (td, J =
7.1, 6.1 Hz, 2H), 1.51−1.34 (m, 2H), 1.31−1.11 (m, 6H),
0.88−0.76 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 140.0,
132.5, 129.0, 127.0, 43.2, 31.2, 29.5, 26.1, 22.4, 13.9; MS (ESI)
m/z: 242.33 (M + H)+.
N-Benzylbenzenesulfonamide (2g).30 222 mg (90%) as
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yellow oil; H NMR (400 MHz, CDCl3): δ 7.89−7.66 (m,
4-((4-Chlorophenyl)sulfonyl)morpholine (2p).19 203 mg
(78%) as a white solid (mp 141−144 °C, lit. 143−144 °C); 1H
NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.7 Hz, 2H), 7.53 (d,
2H), 7.51−7.45 (m, 1H), 7.44−7.35 (m, 2H), 7.19−7.06 (m,
5H), 4.97 (t, J = 6.3 Hz, 1H), 4.04 (d, J = 6.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3): δ 139.9, 136.2, 132.6, 129.0, 128.6,
127.8, 127.8, 127.0, 47.2; MS (ESI) m/z: 248.33 (M + H)+.
N-(Furan-2-ylmethyl)benzenesulfonamide (2h).31 175 mg
(74%) as a white solid (mp 150−152 °C, lit. 149−151 °C); 1H
NMR (400 MHz, CDCl3): δ 7.85−7.80 (m, 2H), 7.59−7.53
(m, 1H), 7.51−7.45 (m, 2H), 7.22 (dd, J = 1.9, 0.9 Hz, 1H),
6.20 (dd, J = 3.2, 1.9 Hz, 1H), 6.07 (dd, J = 3.3, 0.8 Hz, 1H),
4.87 (t, J = 6.3 Hz, 1H), 4.20 (dd, J = 6.1, 0.7 Hz, 2H); 13C
NMR (100 MHz, CDCl3): δ 149.3, 142.5, 139.7, 132.6, 129.0,
127.0, 110.4, 108.3, 40.1; MS (ESI) m/z: 238.03 (M + H)+.
N-((Adamantan-1-yl)methyl)benzenesulfonamide (2i).
J = 8.7 Hz, 2H), 3.80−3.65 (m, 4H), 3.04−2.94 (m, 4H); 13
C
NMR (100 MHz, CDCl3): δ 139.7, 133.8, 129.4, 129.2, 66.0,
45.9; MS (ESI) m/z: 262.71 (M + H)+.
4-((4-Methoxyphenyl)sulfonyl)morpholine (2q).19 190 mg
(74%) as a white solid (mp 111−114 °C, lit. 112−114 °C); 1H
NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.9 Hz, 2H), 7.01 (d,
J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.80−3.62 (m, 4H), 3.02−2.88
(m, 4H); 13C NMR (100 MHz, CDCl3): δ 163.1, 129.9, 126.3,
114.2, 66.0, 55.6, 45.9; MS (ESI) m/z: 258.30 (M + H)+.
4-(o-Tolylsulfonyl)morpholine (2r).16c 178 mg (74%) as a
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234 mg (77%) as a white solid (mp 134−136 °C); H NMR
white solid (mp 88−91 °C, lit. 89−91 °C); H NMR (400
(400 MHz, CDCl3): δ 7.91−7.79 (m, 2H), 7.62−7.45 (m,
3H), 4.79 (t, J = 6.8 Hz, 1H), 2.56 (d, J = 6.8 Hz, 2H), 1.94 (d,
J = 3.2 Hz, 3H), 1.72−1.63 (m, 3H), 1.61−1.51 (m, 3H), 1.43
(d, J = 2.9 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 140.0,
132.4, 129.0, 126.9, 54.8, 39.8, 36.7, 33.0, 28.0; HRMS (ESI)
calculated for [M + H]+ C17H24NO2S, 306.1522; found,
306.1520.
MHz, CDCl3): δ 7.89 (dd, J = 8.2, 1.4 Hz, 1H), 7.48 (td, J =
7.5, 1.4 Hz, 1H), 7.33 (dddt, J = 8.0, 4.3, 3.1, 0.7 Hz, 2H),
3.97−3.52 (m, 4H), 3.25−2.98 (m, 4H), 2.64 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 138.1, 134.7, 133.1, 132.9, 130.4,
126.1, 66.3, 45.2, 20.9; MS (ESI) m/z: 242.31 (M + H)+.
4-((2,4-Dichlorophenyl)sulfonyl)morpholine (2s). 275 mg
(93%) as yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J
F
Org. Process Res. Dev. XXXX, XXX, XXX−XXX