1086
B. Gopishetty et al. / Tetrahedron: Asymmetry 22 (2011) 1081–1086
(50 mL), brine (50 mL), dried over Na2SO4, and the solvent was
removed under reduced pressure. The residue was purified by col-
umn chromatography using 5% ethyl acetate in hexanes to give
by column chromatography using 15–20% ethyl acetate in hexanes
to give trans-compound 17 (1.1 g, 89%) as a white solid. Mp = 99–
101 °C. ½a 2D5
ꢂ
¼ ꢀ58:6 (c 0.5, CH3OH). 1H NMR (400 MHz, CDCl3): d
compound 13 (2.4 g, 84%) as a thick syrup. ½a D25
ꢂ
¼ þ23:6 (c 1.0,
1.66–1.74 (m, 1H), 1.86–1.92 (m, 1H), 3.28 (t, J = 4.0 Hz, 1H), 3.34
(m, 1H), 3.82 (d, J = 9.2 Hz, 1H), 3.95 (d, J = 13.6 Hz, 1H), 4.14 (dt,
J = 2.4, 10.0 Hz, 1H), 4.22 (dd, J = 4.0, 13.6 Hz, 1H), 7.16–7.36 (m,
10H).13C NMR (100 MHz, CDCl3): d 30.53, 51.48, 57.37, 66.27,
71.86, 126.66, 126.93, 128.53, 128.65, 128.90, 141.85, 142.35.
CH3OH). 1H NMR (400 MHz, CDCl3): d 2.16–2.24 (m, 1H), 2.30–
2.38 (m, 1H), 3.69 (dd, J = 5.6, 12.4 Hz, 1H), 3.92 (dd, J = 5.6,
12.4 Hz, 1H), 4.00–4.10 (m, 2H), 4.95–5.10 (m, 4H), 5.62–5.73 (m,
1H), 5.82–5.94 (m, 1H), 7.16–7.42 (m, 10H). 13C NMR (100 MHz,
CDCl3): d 37.32, 56.27, 71.73, 81.87, 116.66, 117.59, 126.49,
126.63, 128.39, 128.70, 128.86, 129.41, 134.92, 135.25, 142.28,
142.91.
4.15. (2S,4R,5R)-2-Benzhydryl-5-((4-methoxybenzyl)amino)-
tetrahydro-2H-pyran-4-ol 18 (D-142)
4.12. (S)-2-Benzhydryl-3,6-dihydro-2H-pyran 14
A mixture of epoxide 17 (0.5 g, 1.88 mmol) and 4-methoxy ben-
zylamine (4.90 mL, 37.57 mmol) in ethanol (20 mL) was refluxed
overnight under a nitrogen atmosphere. The solvent was removed
under reduced pressure and the residue was purified by column
chromatography using 5% methanol in ethyl acetate to give
To a stirred solution of compound 13 (2.0 g, 7.18 mmol) in
anhydrous benzene (75 mL) was added a 1st generation Grubbs
catalyst (0.12 g, 0.14 mmol) under a nitrogen atmosphere. The
reaction mixture was slowly heated at reflux and the reflux was
continued for 2 h. After cooling to room temperature, the solvent
was removed under reduced pressure. The residue was purified
by column chromatography using 5% ethyl acetate in hexanes to
give compound 14 (1.5 g, 83%) as a white solid. Mp = 74–76 °C.
compound 18 (D-142) (0.58 g, 76%) as
a
white solid.
½
a 2D5
ꢂ
¼ ꢀ72:6 (c 0.5, CH3OH). 1H NMR (400 MHz, CDCl3): d 1.43
(dt, J = 3.6, 13.6 Hz, 1H), 1.60 (br s, 2H), 1.73 (dt, J = 3.2, 13.6 Hz,
1H), 2.44 (d, J = 2.4 Hz, 1H), 3.66 (d, J = 12.8 Hz, 2H), 3.74–3.84
(m, 5H), 3.90 (dd, J = 2.8, 12.4 Hz, 1H), 3.93–3.98 (m, 2H), 4.50
(dt, J = 2.4, 10.4 Hz, 1H), 6.85 (d, J = 8.8 Hz, 2H), 7.12–7.38 (m,
12H). 13C NMR (100 MHz, CDCl3): d 33.37, 50.71, 55.21, 56.41,
56.51, 64.75, 67.30, 73.53, 113.77, 126.25, 126.45, 128.32, 128.35,
128.37, 128.57, 129.22, 132.21, 142.01, 142.11, 158.62. The prod-
uct was converted into the corresponding mesylate salt; mp:
162–164 °C. Anal. Calcd for C27H33NO6Sꢃ0.4H2O: C, 63.98; H,
6.72; N, 2.76. Found: C, 64.02; H, 6.59; N, 2.79.
½
a 2D5
ꢂ
¼ ꢀ94:6 (c 0.5, CH3OH). 1H NMR (400 MHz, CDCl3): d 1.88–
1.96 (m, 1H), 2.12–2.24 (m, 1H), 4.10 (d, J = 9.2 Hz, 1H), 4.26–
4.38 (m, 2H), 4.41 (dt, J = 2.8, 9.6 Hz, 1H), 5.80–5.90 (m, 2H),
7.26–7.50 (m, 10H). 13C NMR (100 MHz, CDCl3): d 30.33, 57.58,
66.53, 75.59, 124.70, 126.52, 126.64, 126.88, 128.71, 128.74,
128.88, 128.91, 142.59, 142.76.
4.13. (2S,4R,5R)-2-Benzhydryl-5-bromotetrahydro-2H-pyran-4-
ol 16
Acknowledgment
Into a stirred solution of compound 14 (1.38 g, 5.51 mmol) in
1:1 mixture of H2O/dioxane (30 mL) was added N-bromoacetamide
(1.14 g, 8.27 mmol) portion wise. After stirring for 4 h at room tem-
perature, the reaction mixture was diluted with ether (75 mL), and
the organic layer was washed with saturated NaHCO3 (50 mL)
solution. The aqueous layer was extracted additionally with ether
(2 ꢁ 50 mL). The combined organic layer was washed with water
(40 mL), brine (40 mL), dried over Na2SO4, and the solvent was re-
moved under reduced pressure. The residue was purified by col-
umn chromatography using 15% ethyl acetate in hexanes to give
compound 16 (1.61 g, 84%) as a white solid. Mp = 54–56 °C.
This work was supported by National Institute of Mental
Health/National Institute of Health MH084888 (A.K.D.).
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¼ ꢀ114:4 (c 0.5, CH3OH). 1H NMR (400 MHz, C6D6): d 0.86
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