Synthesis of 1-hydroxy-phenethylamine derivatives
841
70%) as an oil. [α]2D5.8 = −37.4 (c, 3.0 in CHCl3);
IR (neat): 3520, 2955, 2935, 2837, 1612, 1514, 1454,
1359, 1249, 1176 cm−1; 1H NMR (500 MHz, CDCl3):
δ 2.43 (s, 3H), 3.80 (s, 3H), 3.83–3.86 (m, 2H), 3.88 (s,
3H), 3.90 (s, 3H), 3.97 (dd, J = 2.5, 9.5 Hz, 1H), 4.20
(d, J = 11.0 Hz, 1H), 4.36–4.40 (m, 2H), 6.84–6.87
(m, 5H), 7.16 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.0 Hz,
2H), 7.73 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3): δ 21.8, 55.4, 56.0, 56.1, 69.9, 70.6, 73.5, 80.6,
110.3, 111.4, 114.0, 114.1, 120.2, 128.0, 128.1, 129.7,
129.8, 129.9, 130.0, 132.9, 144.9, 149.4, 149.5, 159.6;
HRMS: calcd for C26H30O8SNa [M+Na]+ 525.1559,
found 525.1559.
(neat): 3009, 2935, 2862, 1612, 1514, 1464, 1249,
1
1163 cm−1; H NMR (500 MHz, CDCl3): δ 1.30–1.34
(m, 2H), 1.40–1.56 (m, 8H), 3.45 (dd, J = 6.5, 8.5 Hz,
1H), 3.56–3.59 (m, 1H), 3.72 (s, 3H), 3.79 (s, 3H), 3.81
(s, 3H), 4.13–4.16 (m, 1H), 4.25 (dd, J = 6.5, 14 Hz,
1H), 4.44-4.52 (m, 2H), 6.76-6.84 (m, 5H), 7.16 (d,
J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 23.9,
24.1, 25.3, 35.3, 36.4, 55.4, 55.9, 56.0, 65.8, 69.8, 78.8,
81.8, 110.6, 110.7, 111.0, 113.8, 113.9, 114.1, 128.7,
129.6, 130.4, 130.7, 149.1, 149.2, 159.3; HRMS: calcd
for C25H32O6Na [M+Na]+ 451.2097, found 451.2098.
2.11 Synthesis of (2R,3R)-3-(4-methoxybenzyloxy)-3-
(3,4-dimethoxyphenyl)propane-1,2-diol (4b)
2.13 Synthesis of (1R,2R)-1-(4-methoxybenzyloxy)-1-
(3,4-dimethoxyphenyl)propan-2-ol (6b)
The compound 3b (1.4 g, 3.27 mmol) was stirred
with 80% aqueous acetic acid (5 mL) at 40◦C for 2 h
(monitored by TLC). Acetic acid was removed under
reduced pressure and co-evaporated with toluene. The
crude residue obtained was chromatographed (20%
ethyl acetate in light petroleum) over silica gel to afford
the pure diol 4b (800 mg, 70%) as a viscous liquid.
[α]2D5.6 = −63.4 (c, 5.2 in CHCl3); IR (neat): 3464,
A suspension of LiAlH4(5.0 mmol) in THF (5 mL) was
added drop-wise to the stirred solution of compound
5b (800 mg, 1.6 mmol) in THF (5 mL) at 0◦C under
N2. Then the reaction mixture was stirred for 45 min at
room temperature. Then, 0.5 mL of MeOH was added
to the reaction mixture followed by the addition of a
saturated aqueous solution of sodium potassium tartrate
(10 mL) and excess of diethyl ether (40 mL). The stir-
ring was continued until complete precipitation at room
temperature. The solids were filtered off and the fil-
trate was washed successively with aqueous 10% HCl,
water (10 mL) and brine (10 mL), and finally dried
over Na2SO4. The organic solvent was evaporated under
reduced pressure to afford the alcohol 6b (420 mg,
80%) as an oil.
1
2958, 2837, 1514, 1464, 1251, 1030 cm−1; H NMR
(500 MHz, CDCl3): δ 3.34 (dd, J = 5.0, 11.0 Hz, 1H),
3.51 (dd, J = 3.5, 12.0 Hz, 1H), 3.73–3.78 (m, 1H),
3.80 (s, 3H), 3.88 (s, 3H), 3.89 (s, 3H), 4.21 (d, J =
11.0 Hz, 1H), 4.33 (d, J = 8.0 Hz, 1H), 4.41 (d, J =
11.0 Hz, 1H), 6.86–6.91 (m, 5H), 7.19 (d, J = 8.5 Hz,
2H); 13C NMR (125 MHz, CDCl3): δ 55.4, 56.0, 56.1,
62.6, 70.3, 75.7, 81.7, 110.2, 111.2, 114.1, 120.5, 129.7,
129.8, 129.9, 130.5, 149.2, 149.4, 159.5; HRMS: calcd
for C19H24O6 [M+Na]+ 371.1471, found 371.1472.
2.13a [α]2D5.8 = 68.7 (c, 2.2 in CHCl3); IR (neat):
1
3550, 2935, 2837, 1519, 1467, 1248 cm−1; H NMR
2.12 Synthesis of (2R,3R)-3-(4-methoxybenzyloxy)-2-
hydroxy-3-(3,4-dimethoxyphenyl)propyl
4-methylbenzenesulphonate (5b)
(500 MHz, CDCl3): δ 0.95 (d, J = 6.5 Hz, 3H), 3.80 (s,
3H), 3.83–3.87 (m, 1H), 3.89(s, 3H), 3.90 (s, 3H), 3.98
(d, J = 8.5 Hz, 1H), 4.20 (d, J = 11.0 Hz, 1H), 4.38
(d, J = 11.5 Hz, 1H), 6.86–6.90 (m, 5H), 7.20 (d, J =
8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 18.2, 29.8,
55.4, 56.0, 56.1, 70.3, 71.5, 86.8, 110.3, 111.1, 114.0,
114.1, 120.7, 129.8, 130.2, 131.3, 149.2, 149.4, 159.5;
HRMS: calcd for C19H25O5 [M+H]+ 333.1702, found
333.1693.
To a stirred solution of 4b (800 mg, 2.3 mmol) and
excess of pyridine (3 mL) in dry CH2Cl2 (20 mL) at
0◦C was added p-toluenesulphonyl chloride (530 mg,
2.75 mmol) in portions during 30 min under N2. After
stirring for another 12 h at room temperature, the
mixture was poured into ice-water. The organic layer
was separated and the aqueous portion was extracted
with CH2Cl2 (3 × 50 mL). The combined organic
extract was washed successively with aqueous 10% HCl
(5 mL), water (5 mL) and brine (5 mL), and finally dried
(Na2SO4). Removal of the solvent under reduced pres-
2.14 Synthesis of ((R)-2,2-cyclohexylidine-1,
3-dioxolan-4-yl)methyl 4-methylbenzenesulphonate
(2c)
sure followed by column chromatography of the residue To a stirred solution of (R)-2,3-O-cyclohexylidene-
(10% ethyl acetate in light petroleum) over silica gel glyceraldehyde (B) (850 mg, 5 mmol) in MeOH (8 mL)
afforded the monotosylated derivative 5b (810 mg, NaBH4 (290 mg, 7.5 mmol) was added portion-wise