Molecules 2020, 25, 2484
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133.9, 130.0, 129.0, 128.5, 127.5, 111.2, 108.5, 102.9, 69.1, 62.7; ESI-HRMS (M + H)+ m/z calcd for
C21H19O5S 383.0953, found 383.0914.
3.2.12. (R)-(1-(4-((3-((Phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-2-yl)methanol (2)
Compound 22 (63 mg, 0.17 mmol) was dissolved in 1,2-dicholroethane (5 mL), and (R)-(-)-
prolinol (52 mg, 0.516 mmol) and sodium triacetoxyborohydride (73 mg, 0.34 mmol) were added
thereto. The mixture was stirred for 12 h at room temperature. The reaction was terminated with
water and EtOAc, dried over MgSO4 and concentrated under reduced pressure. The mixture was
separated by column chromatography (CH2Cl2:MeOH = 5:1) to give compound 2 (46 mg, 60%) [15]:
1H-NMR (500 MHz, CDCl3) δ 7.63 (dd, J = 8.4, 1.2 Hz, 2H), 7.61–7.57 (m, 1H), 7.45 (d, J = 7.6 Hz, 2H),
7.43 (d, J = 7.6 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.15–7.10 (m, 1H), 6.89 (ddd, J = 8.3, 2.5, 0.8 Hz, 1H),
6.74–6.70 (m, 1H), 6.62 (d, J = 7.6 Hz, 1H), 4.93 (s, 2H), 4.25 (s, 2H), 4.14 (d, J = 13.1 Hz, 1H), 3.70 (dt, J
= 16.6, 8.3 Hz, 2H), 3.58 (dd, J = 11.8, 3.9 Hz, 1H), 3.18–3.16 (m, 1H), 3.11–3.01 (m, 1H), 2.53 (dd, J =
16.7, 8.6 Hz, 1H), 1.97 (ddd, J = 15.8, 9.6, 5.8 Hz, 2H), 1.84 (ddtd, J = 15.8, 12.3, 8.4, 4.6 Hz, 4H); 13C-
NMR (125 MHz, CDCl3) δ 158.7, 138.0, 133.9, 130.0, 129.7, 129.5, 129.0, 128.7, 127.9, 123.6, 117.0, 115.8,
69.6, 62.9, 61.5, 58.6, 54.3, 27.2, 23.5; ESI-HRMS (M + H)+ m/z calcd for C26H30NO4S 452.1896, found
452.1877.
3.2.13. (S)-1-(4-((3-((Phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-3-ol (3)
Using compound 22 (63 mg, 0.17 mmol) and (S)-(-)-3-hydroxy pyrrolidine (45 mg, 0.516 mmol),
compound 3 (38 mg, 52%) was obtained by the same method as the synthesis method of compound
1
2: H-NMR (500 MHz, CDCl3) δ 7.63 (dd, J = 8.4, 1.2 Hz, 2H), 7.61–7.57 (m, 1H), 7.46–7.44 (m, 2H),
7.45–7.42 (m, 2H), 7.16–7.09 (m, 1H), 6.92–6.85 (m, 1H), 6.74–6.70 (m, 1H), 6.61 (d, J = 7.6 Hz, 1H), 4.92
(s, 2H), 4.40–4.39 (m, 1H), 4.25 (s, 2H), 3.90 (d, J = 7.9 Hz, 2H), 3.17–3.07 (m, 1H), 2.95 (d, J = 11.1 Hz,
1H), 2.88 (dd, J = 11.1, 5.0 Hz, 1H), 2.72 (dd, J = 15.2, 9.2 Hz, 1H), 2.25–2.13 (m, 1H), 1.95–1.82 (m, 1H);
13C-NMR (125 MHz, CDCl3) δ 158.7, 137.9, 137.0, 133.9, 130.0, 129.7, 129.4, 129.2, 128.7, 127.9, 123.7,
117.1, 115.7, 70.5, 69.6, 62.9, 62.0, 59.5, 52.4, 34.3; ESI-HRMS (M + H)+ m/z calcd for C25H28NO4S 438.1739,
found 438.1702.
3.2.14. 1-(4-((3-((Phenylsulfonyl)methyl)phenoxy)methyl)benzyl)piperidin-4-ol (4)
Using compound 22 (63 mg, 0.17 mmol) and 4-hydroxypiperidine (52 mg, 0.516 mmol),
1
compound 4 (53 mg, 69%) was obtained by the same method as the synthesis of compound 2: H-
NMR (500 MHz, CDCl3) δ 7.63–7.60 (m, 2H), 7.58 (dd, J = 10.6, 4.4 Hz, 1H), 7.43 (dd, J = 8.1, 7.6 Hz,
2H), 7.40 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 7.9 Hz, 1H), 6.94–6.87 (m, 1H), 6.75–
6.69 (m, 1H), 6.60 (d, J = 7.6 Hz, 1H), 4.92 (s, 2H), 4.25 (s, 2H), 3.77–3.74 (m, 1H), 3.68 (s, 2H), 2.94–2.82
(m, 1H), 2.57–2.44 (m, 2H), 2.03–1.90 (m, 2H), 1.71–1.57 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 158.7,
137.9, 136.5, 133.9, 130.2, 129.7, 129.5, 129.1, 128.8, 127.7, 123.6, 117.0, 115.8, 69.7, 62.9, 61.9, 50.7, 33.0;
ESI-HRMS (M + H)+ m/z calcd for C26H30NO4S 452.1896, found 452.1890.
3.2.15. (R)-(1-(4-((3-Fluoro-5-((phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-2-
yl)methanol (5)
Using compound 23 (84 mg, 0.22 mmol) and (R)-(-)-prolinol (66 mg, 0.656 mmol), compound 5
(72 mg, 70%) was obtained by the same method as the synthesis of compound 2: 1H-NMR (500 MHz,
CDCl3) δ 7.65 (dd, J = 8.3, 1.2 Hz, 2H), 7.64–7.59 (m, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.49–7.44 (m, 2H),
7.36 (d, J = 8.0 Hz, 2H), 6.60 (dt, J = 10.4, 2.3 Hz, 1H), 6.52–6.51 (m, 1H), 6.40–6.34 (m, 1H), 4.92 (s, 2H),
4.29 (d, J = 13.1 Hz, 1H), 4.21 (s, 2H), 3.90 (d, J = 13.1 Hz, 1H), 3.81–3.66 (m, 2H), 3.33–3.22 (m,2H),
2.74–2.66 (m, 1H), 2.04–1.79 (m, 4H); 13C-NMR (125 MHz, CDCl3) δ 164.2, 162.2, 159.8, 137.8, 137.0,
134.1, 130.8, 129.2, 128.6, 127.9, 113.1, 110.6, 110.5, 103.4, 103.2, 69.8, 67.4, 62.5, 61.3, 58.7, 54.0, 53.6,
50.7, 26.8, 23.4; ESI-HRMS (M + H)+ m/z calcd for C26H29FNO4S 470.1801, found 470.1819.