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T. Nakamura et al. / Tetrahedron: Asymmetry 17 (2006) 2781–2792
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was replaced with hydrogen. After stirring for 22 h at room
temperature, the reaction mixture was filtered through
Celite. The filtrate was evaporated in vacuo to give a white
solid, which was dissolved in DMF (0.5 ml). To this solu-
tion were added 1-iodoheptane (11 ll, 0.064 mmol) and
potassium carbonate (14 mg, 0.10 mmol). After stirring
for 3 h at 60 ꢁC, the reaction mixture was cooled to room
temperature and poured into water, and extracted with
Et2O. The combined organic layer was washed with brine,
dried over MgSO4 and filtered. The filtrate was evaporated
in vacuo, and the residue obtained was purified by
chromatography on a silica gel column (eluent, n-hexane–
AcOEt = 4:1–2:1) to afford tert-butyl [(1R)-3-[4-(heptyl-
oxy)phenyl]-1-(hydroxymethyl)-1-methylpropyl]carbamate
(8.2 mg, 65%) as a white crystalline solid. 1H NMR
(400 MHz, CDCl3): d 7.08 (d, 2H, J = 8.6 Hz), 6.81 (d,
2H, J = 8.6 Hz), 4.62 (br s, 1H), 4.08 (br, 1H), 3.92 (t, 2H,
J = 6.6 Hz), 3.70 (dd, 1H, J = 11.3, 7.0 Hz), 3.63 (dd,
1H, J = 11.3, 5.1 Hz), 2.61 (dt, 1H, J = 12.1, 5.5 Hz),
2.52 (dt, 1H, J = 13.7, 5.5 Hz), 2.02 (dt, 1H, J = 13.7,
5.1 Hz), 1.84 (dt, 1H, J = 13.7, 5.5 Hz), 1.78 (quintet, 2H,
J = 7.8 Hz), 1.49–1.22 (m, 17H), 1.22 (s, 3H), 0.89 (t, 3H,
J = 7.0 Hz); MS (FAB) m/z: 394 (M+H)+. To a solution
of tert-butyl [(1R)-3-[4-(heptyloxy)phenyl]-1-(hydroxy-
methyl)-1-methylpropyl]carbamate (8.2 mg, 0.021 mmol)
in MeOH (1 ml) was added 4 M solution of HCl in dioxane
(0.5 ml) at room temperature. After stirring for 3 h at room
temperature, the reaction mixture was evaporated in vacuo
to give a white solid, which was dissolved in AcOEt (1 ml).
To this solution was added satd NaHCO3 (0.5 ml), and this
mixture was stirred for 1 h at room temperature. The
resulting mixture was poured into water, and extracted
with AcOEt. The combined organic layer was washed with
brine, dried over MgSO4 and filtered. The filtrate was evap-
´
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´
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orated in vacuo to give compound 4 (3.5 mg, 56%) as a pale
24
yellow solid. ½aꢁD ¼ ꢀ5:6 (c 0.21, CHCl3); IR (KBr): 3235,
2925, 2856, 1566, 1513 cmꢀ1
;
1H NMR (400 MHz,
CD3OD): d 7.11 (d, 2H, J = 8.3 Hz), 6.81 (d, 2H, J = 8.3 Hz),
3.93 (t, 2H, J = 6.3 Hz), 3.43 (d, 1H, J = 10.7 Hz), 3.38
(d, 1H, J = 10.7 Hz), 2.58 (t, 2H, J = 8.8 Hz), 1.78–1.64
(m, 4H), 1.50–1.43 (m, 2H), 1.42–1.29 (m, 6H), 1.14 (s, 3H),
0.92 (t, 3H, J = 6.8 Hz); MS (FAB) m/z: 294 (M+H)+.
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