5040
M.N. Patil et al. / Tetrahedron 66 (2010) 5036e5041
temperature for 1 h, to obtain one of the diastereomeric salts as
MeOH/EtOAc) 0.45; vmax (CHCl3): 3388, 3018, 1215 cmꢀ1 1H NMR
;
white precipitate. The mixture was filtered to obtain solid salt (2 g,
(200 MHz, CDCl3) 7.24e7.42 (m, 10H), 4.65 (s, 1H), 4.04 (s, 1H), 1.00
(s, 3H), 0.67 (s, 3H); 13C NMR (50.32 MHz, CDCl3) 141.7, 141.1, 128.2,
128.1, 127.6, 127.2, 126.8, 79.5, 65.9, 40.0, 23.6, 20.7.
44%), mp 196e197 ꢁC, [
a
]
D
26 e66 (c¼1, MeOH). The second isomer of
the salt was isolated from mother liquor by evaporation followed by
recrystallization from ethanol: ethyl acetate (1:9), (1.9 g, 42%), mp
160e161 ꢁC, [
a
]
D
ꢀ42 (c 1, MeOH). Basification of the salts was
7.1.10.1. Resolution of (ꢂ)-(2). The same procedure was fol-
lowed as described for the resolution of (ꢂ)-1.
carried out using aqueous NH3 to provide the corresponding opti-
cally pure aminoalcohols. (þ)-1 Isomer of aminoalcohol was
obtained from the precipitated salt while (ꢀ)-1 isomer was isolated
from the salt left in the filtrate.
Precipitated salt 42%yield, mp 175e177 ꢁC, [
Salt from filtrate 39% yield, mp 160e162 ꢁC, [
a
]
26 ꢀ60 (c 1, MeOH).
D
a]
26 ꢀ44 (c 1, MeOH).
D
Basification was carried out as described for above.
(1R,3S)-(þ)-1; 44% yield, mp 169e171 ꢁC, [
a]
26 þ42 (c 1, CHCl3),
(1R,3R)-(þ)-2; 42% yield, mp 142e143 ꢁC, [
a
]
26 þ40 (c 1, CHCl3),
D
D
>99:1 er (Kromasil-5-Amycoat column, 2-propanol/PE/TFA).
>99:1 er (Kromasil-5-Amycoat column, 2-propanol/PE/TFA).
26
(1S,3R)-(ꢀ)-1; 42% yield, mp 170e171 ꢁC, [
a
]
26 ꢀ42 (c 1, CHCl3),
(1S,3S)-(-)-2; 42% yield, mp 141e142 ꢁC, [
a
]
ꢀ40 (c 1, CHCl3),
D
D
>99:1 er (Kromasil-5-Amycoat column, 2-propanol/PE/TFA).
>99:1 er (Kromasil-5-Amycoat column, 2-propanol/PE/TFA).
7.1.6. syn-(ꢂ)-3-Hydroxy-2,2-dimethyl-1,3-diphenylpropyl benzoate
(8). The diol 7 (as a mixture of syn/anti in 92:8, 6.4 g, 25 mmol) was
dissolved in anhydrous CH2Cl2 (75 mL). To the stirred solution,
pyridine (2 mL, 25 mmol) followed by benzoyl chloride (2.9 mL,
25 mmol) were added dropwise. It was then stirred for 16 h at room
temperature. The reaction mixture was diluted with CH2Cl2
(100 mL) and washed with 1 N HCl, water, NaHCO3, water, and
brine, dried over Na2SO4, and concentrated under reduced pres-
sure. The residue was purified by ‘flash chromatography’ on silica
gel (200e400 mesh) using ethyl acetate/petroleum ether as the
eluent followed by crystallization from ethyl acetate/petroleum
ether (1:9) to obtain 8 as a white solid (6.4 g, 71%), >99:1 dr (by 1H
NMR), mp 151e153 ꢁC; [Found: C, 80.26; H, 6.38. C24H24O3 requires
C, 79.97; H, 6.71%]; Rf (10% EtOAc/PE) 0.32; vmax (CHCl3): 3610,
7.2. General procedure for the preparation of N-methyl -1,3-
aminoalcohol
A suspension of 1 (1.28 g, 5 mmol), K2CO3 (1.04 g, 7.5 mmol),
methyl iodide (0.78 g, 5.5 mmol) in acetonitrile (20 mL) was stirred
at room temperature for 16 h. The reaction mixture was filtered and
concentrated under reduced pressure. The residue was purified by
‘flash chromatography’ on silica gel (200e400 mesh) using ethyl
acetate/petroleum ether as the eluent followed by crystallization
from toluene.
7.2.1. (1S,3R)-2,2-Dimethyl-3-(methylamino)-1,3-diphenylpropan-1-ol,
(ꢀ)-12. Yield 75%, mp 118e120 ꢁC; [Found: C, 79.93; H, 8.44; N,
5.23. C18H232N6 O requires C, 80.26; H, 8.61; N, 5.20%]; Rf (20% EtOAc/
1720 cmꢀ1
;
1H NMR (200 MHz, CDCl3) 7.26e8.11 (m, 15H), 6.10 (s,
PE) 0.2; [
a
]
ꢀ80 (c 1, CHCl3); vmax (CHCl3): 3019, 1454 cmꢀ1
;
1H
D
1H), 4.49 (s, 1H), 2.00 (s, 1H), 1.19 (s, 3H), 0.84 (s, 3H); 13C NMR
(50.32 MHz, CDCl3) 165.3, 141.2, 138.1, 132.9, 130.6, 129.6, 128.4,
127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 80.3, 77.8, 43.1, 19.2, 18.0.
NMR (200 MHz, CDCl3) 7.20e7.39 (m, 10H), 4.82 (s, 1H), 3.63 (s, 1H),
2.27 (s, 3H), 0.90 (s, 3H), 0.36 (s, 3H);13C NMR (50.32 MHz, CDCl3)
142.2, 133.0, 131.2, 128.0, 127.6, 127.5, 127.4, 126.8, 84.0, 73.9, 43.6,
42.0, 26.1, 23.9.
7.1.7. syn-(ꢂ)-3-Chloro-2,3-dimethyl-1,3-diphenylpropylbenzoate(9).
The same procedure was followed as described for the compound 4.
Yield 80%, >99:1 dr, mp 136e137 ꢁC; [Found: C, 75.76; H, 6.33.
C24H23ClO2 requires C, 76.08; H, 6.12%]; Rf (10% EtOAc/PE) 0.54; vmax
(CHCl3): 3018,1722,1452 cmꢀ1; 1H NMR (200 MHz, CDCl3) 7.27e8.12
(m, 15H), 5.91 (s, 1H), 4.84 (s, 1H), 1.35 (s, 3H), 0.95 (s, 3H); 13C NMR
(50.32 MHz, CDCl3) 165.0,138.0,137.4,133.2,130.3,129.0,128.5,128.2,
128.1, 128.0, 127.9, 127.8, 79.9, 69.7, 44.4, 19.8, 19.4.
7.2.2. (1S,3S)-2,2-Dimethyl-3-(methylamino)-1,3-diphenylpropan-1-ol,
(ꢀ)-13. Yield 73%, mp 132e134 ꢁC; [Found: C, 80.36; H, 8.77; N,
4.91. C18H23NO requires C, 80.26; H, 8.61; N, 5.20%]; Rf (20% EtOAc/
26
PE) 0.2; [
a
]
ꢀ30 (c 1, CHCl3). vmax (CHCl3): 3000, 1495 cmꢀ1
;
1H
D
NMR (200 MHz, CDCl3) 7.18e7.32 (m, 10H), 4.57 (s, 1H), 3.55 (s, 1H),
2.25 (s, 3H), 0.99 (s, 3H), 0.70 (s, 3H); 13C NMR (50.32 MHz, CDCl3)
141.5, 138.5, 128.4, 128.2, 127.5, 127.3, 127.1, 85.0, 75.4, 41.0, 34.0,
24.9, 12.4.
7.1.8. anti-(ꢂ)-3-Azido-2,3-dimethyl-1,3-diphenylpropyl benzoate (10).
The same procedure was followed as described for the compound 5.
Yield 78%, >99:1 dr, mp 154e155 ꢁC; [Found: C, 75.06; H, 5.76; N,
10.75. C24H23N3O2 requiresC, 74.78;H, 6.01;N,10.90%]; Rf (10%EtOAc/
7.3. General procedure for the preparation of N,N-dimethyl -
1,3-aminoalcohol
PE) 0.54; vmax (CHCl3): 3018, 2104, 1720 cmꢀ1
;
1H NMR (200 MHz,
A suspension of 1 (1.28 g, 5 mmol), K2CO3 (2.08 g, 15 mmol),
methyl iodide (1.78 g, 12.5 mmol) in acetonitrile (25 mL) was stir-
red under reflux temperature for 16 h. The product was isolated
and purified as described above.
CDCl3) 7.26e8.18 (m,15H), 6.2 (s,1H), 4.82 (s,1H), 0.90 (s, 3H), 0.78 (s,
3H); 13C NMR (50.32 MHz, CDCl3) 165.1, 137.7, 136.6, 133.1, 130.3,
129.6,129.0, 128.5,128.1,128.1,128.0,127.9, 79.4, 71.3, 42.2,19.3,18.5.
7.1.9. anti-(ꢂ)-3-Azido-2,3-dimethyl-1,3-diphenylpropan-1-ol (11).
The same procedure was followed as described for the compound 6.
Yield 90%, >99:1 dr, mp 135e136 ꢁC; [Found: C, 72.63; H, 6.80; N,
15.20. C17H19N3O requires C, 72.57; H, 6.81; N,14.94%]; Rf (10% EtOAc/
7.3.1. (1S,3R)-2,2-Dimethyl-3-(dimethylamino)-1,3-diphenylpropan-
1-ol, (ꢀ)-14. Yield 76%, mp 106e107 ꢁC; [Found: C, 80.63; H, 9.15;
N, 4.84. C19H25NO requires C, 80.52; H, 8.89; N, 4.94%]; Rf (20%
EtOAc/PE) 0.24;
[a
]
ꢀ42 (c 1, CHCl3); vmax (CHCl3): 3016,
D
PE) 0.42; vmax (CHCl3): 3608, 3018, 2104 cmꢀ1
;
1H NMR (200 MHz,
1465 cmꢀ1; 1H NMR (200 MHz, CDCl3) 7.26e7.39 (m, 10H), 4.80 (s,
1H), 3.75 (s, 1H), 2.35 (s, 6H), 1.27 (s, 3H), 0.37 (s, 3H); 13C NMR
(50.32 MHz, CDCl3) 141.1,133.0,131.1,128.5,127.9,127.7,127.2,127.0,
85.8, 81.1, 43.7, 42.1, 25.5, 15.3.
CDCl3) 7.26e7.38 (m,10H), 4.97 (s, 1H, eOH), 4.88 (s, 1H),1.92 (s, 1H),
0.72 (s, 3H), 0.68 (s, 3H); 13C NMR (50.32 MHz, CDCl3) 141.4, 137.0,
129.0, 128.0, 128.0, 127.9, 127.6, 127.4, 78.0, 71.7, 42.2, 19.3, 18.9.
7.1.10. anti-(ꢂ)-3-Amino-2,3-dimethyl-1,3-diphenylpropan-1-ol
(2). The same procedure was followed as described for the com-
pound 1.
7.3.2. (1S,3S)-2,2-Dimethyl-3-(dimethylamino)-1,3-diphenylpropan-
1-ol, (ꢀ)-15. Yield 75%, mp 116e118 ꢁC; [Found: C, 80.35; H, 9.00;
N, 4.76. C19H25NO requires C, 80.52; H, 8.89; N, 4.94%]; Rf (20%
Yield w100%, with >99:1 dr, mp 137e139 ꢁC; [Found: 79.84; H,
8.18; N, 5.33. C17H21NO requires C, 79.96; H, 8.29; N, 5.49%]; Rf (40%
EtOAc/PE) 0.24; [
a]
ꢀ102 (c 1, CHCl3); vmax (CHCl3): 3000,
D
1451 cmꢀ1 1H NMR (200 MHz, CDCl3) 7.14e7.43 (m, 10H), 4.67 (s,
;