The Journal of Organic Chemistry
Note
22
tR(major) = 9.1 min, tR(minor) = 10.6 min); [α]D = +33.0 (c 0.3,
(1S,2R)-2-Amino-1-phenyl-propan-1-ol, (1S,2R)-1b, [(1S,2R)-
(+)-Norephedrine].
CH3OH); ATR-FTIR, ν (cm−1) 3212, 1336, 1176, 1139; H NMR
1
(500 MHz, CDCl3) δ 7.44−7.48 (m, 3H), 7.36−7.40 (m, 2H), 5.84
(d, 1H, J = 5.7 Hz), 4.32−4.40 (m, 2H), 1.02 (d, 3H, J = 6.5 Hz); 13C
NMR (75 MHz, CDCl3) δ 133.1, 129.5, 129.1, 126.1, 88.2, 56.2, 15.7;
HRMS (EI) m/z calcd for C9H11NO3S 213.0460, found 213.0463.
A single recrystallization (EtOAc/n-hexane) of (4R,5S)-7 (96.4% ee)
afforded the optically pure (90%, >99% ee) product.
From >99% ee of (4R,5S)-7. White solid, yield: 75.6% (48 mg); mp
50−53 °C; >99% ee (Chiralcel AD-H, 10% isopropanol/hexanes,
1.0 mL/min, 254 nm, tR(major) = 8.3 min, tR(minor) = 16.4 min);
[α]D22 = +16.9 (c 0.6, CH3OH), lit.31 [α]D26 = +14.0 (c 1.2, CH3OH);
1H NMR (300 MHz, CDCl3) δ 7.27−7.35 (m, 5H), 4.52 (d, 1H, J =
4.8 Hz), 3.15−3.23 (m, 1H), 1.78(br, s, 3H), 0.96 (d, 3H, J = 6.5 Hz);
13C NMR (125 MHz, CDCl3) δ 141.6, 128.3, 127.6, 126.7, 77.7, 52.0,
(4S,5R)-5-(4-Fluoro-phenyl)-4-methyl-[1,2,3]oxathiazolidine 2,2-
dioxide, (4S,5R)-12.
18.4; HRMS (EI) m/z calcd for C9H13NO 151.0997, found 151.0995.
Synthesis of Norpseudoephedine. (4S,5R)-4-Methyl-2,2-dioxo-
5-phenyl-2λ6-[1,2,3]oxathiazolidine-3-carboxylic Acid tert-Butyl
Ester, N-Boc-(4S,5R)-7.
White soild, yield: 83.8% (376 mg); mp 112−114 °C; 92.8% ee
(Chiralcel AD-H, 10% isopropanol/hexanes, 1.5 mL/min, 254 nm,
22
tR(minor) = 9.3 min, tR(major) = 12.1 min); [α]D = −18.0 (c 0.3,
1
CH3OH); ATR-FTIR, ν (cm−1) 3223, 1340, 1179, 1168, 1137; H
NMR (500 MHz, CD3OD) δ 7.41−7.46 (m, 2H), 7.13−7.19 (m, 2H),
5.83 (d, 1H, J = 6.2 Hz), 4.24−4.28 (m, 1H), 0.91 (d, 3H, J = 6.8 Hz);
13C NMR (75 MHz, CD3OD) δ 166.2, 162.9, 131.90, 131.86, 130.0,
129.9, 116.7, 116.4, 89.0, 57.0, 15.4; HRMS (EI) m/z calcd for
C9H10FNO3S 231.0365, found 231.0372.
(4S,5R)-7 (50.3 mg, 0.24 mmol, >99% ee) was dissolved in dry
CH2Cl2. Boc2O (103 mg, 0.48 mmol) and DMAP (3 mg, 0.02 mmol)
were added, and the mixture was stirred at room temperature for 10 min.
After removal of the solvent, the residue was purified by column
chromatography (n-hexane/EA = 10:1) to give the product as white
solid (72.4 mg, 96.3%).
(4S,5R)-4-Ethyl-5-phenyl-[1,2,3]oxathiazolidine 2,2-dioxide,
(4S,5R)-15.
White soild, yield: 96.3% (72.4 mg); mp 102−105 °C; >99% ee
(Chiralcel AD-H, 30% isopropanol/hexanes, 1.0 mL/min, 254 nm,
24
tR(major) = 4.6 min, tR(minor) = 7.3 min); [α]D = −53.0 (c 0.3,
1
CH3OH); ATR-FTIR, ν (cm−1) 2989, 1730, 1364, 1327, 1185; H
NMR (500 MHz, CDCl3) δ 7.44−7.48 (m, 3H), 7.34−7.35 (m, 2H),
5.99 (d, 1H, J = 5.2 Hz), 4.59−4.61 (m, 1H), 1.61 (s, 9H), 1.11 (d,
3H, J = 6.7 Hz); 13C NMR (75 MHz, CDCl3) δ 148.5, 131.5, 129.5,
129.1, 125.5, 85.6, 82.4, 58.7, 28.1, 14.4; HRMS (EI) m/z calcd for
C14H19NO5S 313.0984, found 313.0950.
White soild, yield: 79.0% (327 mg); mp 115−116 °C; 93.4% ee
(Chiralcel AD-H, 10% isopropanol/hexanes, 1.0 mL/min, 254 nm,
22
tR(minor) = 12.0 min, tR(major) = 13.8 min); [α]D = −31.9 (c 0.3,
1
CH3OH); ATR-FTIR, ν (cm−1) 3221, 1339, 1179, 1139, 1123; H
NMR (500 MHz, CDCl3) δ 7.37−7.46 (m, 5H), 5.85 (d, 1H, J = 6.0
Hz), 4.56 (br, d, 1H, J = 8.7 Hz), 4.09−4.13 (m, 1H), 1.16−1.31 (m,
2H), 0.95 (t, 3H, J = 7.3 Hz); 13C NMR (75 MHz, CDCl3) δ 133.3,
129.5, 129.0, 126.3, 88.3, 62.4, 23.3, 11.1; HRMS (EI) m/z calcd for
C10H13NO3S 227.0616, found 227.0624.
(4R,5S)-4-Methyl-2,2-dioxo-5-phenyl-2λ6-[1,2,3]oxathiazolidine-
3-carboxylic Acid tert-Butyl Ester, N-Boc-(4R,5S)-7.
Synthesis of Norephedrine. (1R,2S)-2-Amino-1-phenyl-propan-
1-ol, (1R,2S)-1a, [(1R,2S)-(−)-Norephedrine]. To a suspension of
LiAlH4 (2 M solution in THF, 630 μL, 3 equiv) in THF (1.5 mL),
(4S,5R)-7 (90.0 mg, 0.42 mmol, >99% ee) in THF (3 mL) was added
dropwise at 0 °C. The reaction mixture was stirred at room tem-
perature for 1 h, and then 1 N HCl was added. The mixture was stirred
at 60 °C for 1 h and then cooled to room temperature. 1 N NaOH was
added, and aqueous layer was extracted with CH2Cl2 three times.
The combined organic layers were dried over MgSO4. After removal of
the solvent, the residue was purified by column chromatography
(CH2Cl2/MeOH = 1:1) to give the product as white solid (42 mg,
71.5%).
White soild, yield: 94.0% (71 mg); mp 101−104 °C; >99% ee
(Chiralcel AD-H, 30% isopropanol/hexanes, 1.0 mL/min, 254 nm,
22
tR(minor) = 4.6 min, tR(major) = 7.3 min); [α]D = +51.2 (c 0.3,
1
CH3OH); ATR-FTIR, ν (cm−1) 2991, 1730, 1364, 1327, 1185; H
NMR (300 MHz, CDCl3) δ 7.40−7.46 (m, 3H), 7.30−7.33 (m, 2H),
5.96 (d, 1H, J = 5.2 Hz), 4.56−4.59 (m, 1H), 1.58 (s, 9H), 1.08 (d,
3H, J = 6.7 Hz); 13C NMR (75 MHz, CDCl3) δ 148.5, 131.5, 129.5,
129.1, 125.5, 85.6, 82.4, 58.7, 28.1, 14.4; HRMS (EI) m/z calcd for
C14H19NO5S 313.0984, found 313.0980.
(4S,5S)-2-(tert-Butoxycarbonyl-amino)-1-(benzoyl-oxy)-1-phenyl-
propane, (4S,5S)-9.
White solid, yield: 71.5% (42 mg); mp 51−53 °C; >99% ee
(Chiralcel AD-H, 10% isopropanol/hexanes, 1.0 mL/min, 254 nm,
The mixture of N-Boc-(4S,5R)-7 (30 mg, 0.10 mmol), CsF (22 mg,
0.14 mmol) and benzoic acid (18 mg, 0.14 mmol) in DMF (1 mL)
was stirred at 60 °C for 12 h. After evaporating of the solvent, the
residue was dissolved in the mixture of 1 N HCl (3 mL) and CH2Cl2
(3 mL). The resulting solution was stirred at room temperature for
1 h. The reaction mixture was basified by addition of saturated
NaHCO3 solution and extracted with CH2Cl2 three times and then
22
tR(minor) = 8.3 min, tR(major) = 16.4 min); [α]D = −15.1 (c 0.3,
CH3OH), lit.31 [α]D26 = −14.5 (c 1.2, CH3OH); 1H NMR (500 MHz,
CDCl3) δ 7.29−7.40 (m, 5H), 4.57 (d, 1H, J = 4.8 Hz), 3.22−3.26 (m,
1H), 1.00 (d, 3H, J = 6.5 Hz); 13C NMR (75 MHz, CDCl3) δ 141.3,
128.2, 127.5, 126.5, 77.5, 51.9, 18.2; HRMS (EI) m/z calcd for
C9H13NO 151.0997, found 151.0994.
5458
dx.doi.org/10.1021/jo300867y | J. Org. Chem. 2012, 77, 5454−5460