Organic Syntheses, Vol. 79, pp. 109-115
Checked by Lloyd J. Simons and William R. Roush.
1. Procedure
2. Notes
2. The submitter reports that a second crop of pure
2 (
6.0 g) could be obtained by concentration
and recrystallization of the mother liquors. However, the second crops obtaine by
the checkers were highly colored and were not sufficiently pure for use in the next
step.
3.
Sulfonamide 2
exhibited the following physical and spectroscopic properties:
mp 121-122°C, TLC (silica gel) R
f = 0.28 in 3:1 hexanes
:
ethyl acetate; (1R, 2S)-
2:
[α]D23 −12.4 (c 2.12, CHCl3).
(
1S, 2R)-
2:
[α]D23
+12.8 (c 2.12, CHCl3).
1H NMR (500 MHz, CDCl
3) (concentration dependent;
20 mg/mL) δ: 0.87 (d, 3 H, J = 6.8), 2.30 (s, 3 H),
2.52 (1 H, -OH), 2.66 (s, 6 H), 3.53 (m, 1
H), 4.76 (br,1 H, -NH), 4.82 (d,1 H, J = 8.8),
6.96 (s, 2 H), 7.20-7.36 (m, 5 H); (200 mg/mL) δ: 0.88 (d, 3 H, J = 6.8),
2.32 (s, 3 H), 2.68 ( s, 6 H), 3.08 (1 H, -OH),
3.51 (ddq, 1 H, J = 3.1, 6.8, 9.0), 4.81 (br, 1 H, -NH),
5.23 ( br, 1 H), 6.98 (s, 2 H), 7.20-7.36 (m, 5 H).
13C NMR (125
MHz, CDCl
3, c = 20 mg/mL) δ: 14.3, 20.9,
22.9, 54.6, 75.6, 125.9, 127.5,
128.3, 132.0, 134.2, 138.9, 140.5,
142.2. IR (thin film
from CH
2Cl
2) cm
−1: 3504, 3302,
2981, 1064, 1452, 1320, 1156,
1058, 972, 895, 702, 657.
HRMS-FAB: Calcd for C
18H
24NO
3S [M+H]+, 334.1477
m/z; Found,
334.1478
m/z.
Anal. Calcd for C
18H
23NO
3S: C, 64.84; H, 6.95; N,
4.20. Found: C, 64.94; H, 6.98; N, 4.17.
4. The checkers observed that the reaction is not complete according
to TLC analysis after the prescribed 17-hr reaction period. However, if the reaction
is allowed to proceed for longer reaction times, the dibenzylated product
4
is obtained with correspondingly diminished yields of
3. When the reaction
was terminated after 17 hr, the checkers obtained an
86%
yield of recrystallized
3.

5. The submitter reports that an additional
3.2 g (
15%)
of
3 was isolated by chromatography (Note
1) of the mother
liquor on silica gel (100 g) with
10%
ethyl acetate in
hexane.
The checkers observed that the concentrated mother liquors were not soluble in the
chromatography solvent, so they dissolved the viscous oil in
dichloromethane
(<7 mL) and applied this solution to the column. Once
this material was adsorbed, the column was flushed with
hexanes
(400 mL) to remove the CH
2Cl
2. Elution
of the column with
10% ethyl
acetate-hexanes then provided additional product
2. The
combined yield of
2 obtained by the checkers via the crystallization and chromatography
sequence was
90-93%.
6.
N-Benzylsulfonamide 3
exhibited the following physical and spectroscopic properties:
mp 123-124°C; TLC (silica gel) R
f = 0.48 in
3:1 hexanes :
ethyl acetate;
R
f = 0.15 in 9:1 hexanes :
ethyl acetate; (
1R,
2S)-
3:
[α]D23
−6.3° (c 2.06, CHCl3); (
1S, 2R)-
3:
[α]D23 +6.4° (c 2.05, CHCl3);
1H NMR (500 MHz,
CDCl
3) (concentration dependent; 18 mg/mL) δ: 1.03 (d, 3 H,
J = 7.0), 2.14 (1 H, -OH), 2.29 (s, 3 H),
2.65 (s, 6 H), 3.82 (dq, 1 H, J = 1.9, 7.0), 4.54
(1 H, A of ABq, J
AB = 16.1), 4.77 (1 H, B of ABq, J
AB
= 16.1), 5.00 (br s, 1 H), 6.93 (s, 2 H), 7.04-7.08
(m, 2 H), 7.10-7.36 (m, 8 H); (218 mg/mL) δ: 1.02 (d, 3 H, J = 7.0 ), 2.27
(s, 3 H), 2.34 (1 H, -OH), 2.62 (s, 6 H),
3.82 (dq, 1 H, J = 1.9, 7.0), 4.56 (1 H, A of ABq, J
AB
= 16.1), 4.75 (1 H, B of ABq, J
AB = 16.1 Hz), 4.96
(br s, 1 H), 6.91 (s, 2 H), 7.04-7.08 (m, 2 H), 7.10-7.36
(m, 8 H);
13C
NMR (125 MHz, CDCl
3, 18 mg/mL) δ: 9.8, 20.9,
23.0, 49.1, 59.7, 76.6, 125.5,
127.2, 127.4, 127.7, 128.2, 128.6,
132.2, 133.4, 138.6, 140.2, 142.1,
142.6; IR (film from
CH
2Cl
2) cm
−1: 3502, 2981,
1604, 1454, 1314, 1150, 1022,
924, 855, 699, 658;
HRMS-FAB: Calcd for C
25H
30NO
3S [M+H]
+,
424.1946
m/z;
Found, 424.1947
m/z; Anal. Calcd for C
25H
29NO
3S: C, 70.89;
H, 6.90; N, 3.31; Found: C, 70.91; H, 6.95; N, 3.32.
7. The checkers obtained
1 in
96% yield after recrystallization of the crude product
(see Note
8).
8. (
1R, 2S)- and (
1S, 2R)-
1 exist as polymorphic
forms. Recrystallization from hot
ethyl acetate (4 mL/g of
1)
and
hexane (
ethyl acetate :
hexane
= 1 : 2) afforded higher melting crystals:
mp
124°C,
147-148°C, TLC
(silica gel) R
f = 0.52 in 3:1 hexanes :
ethyl acetate;
R
f = 0.22 in 9:1 hexanes :
ethyl acetate; (
1R,
2S)-
1 [α]D23
+11.1° (c 2.24, CHCl3); (
1S, 2R)-
1:
[α]D23 −11.2° (c 2.38,
CHCl3);
1H
NMR (500 MHz, CDCl
3) δ: 1.01 (t, 3 H, J = 7.4), 1.12
(d, 3 H, J = 7.0), 2.14 (m, 2 H), 2.27 (s, 3 H),
2.51 (s, 6 H), 4.04 (dq, 1 H, J = 4.0, 7.0), 4.60
(1 H, A of ABq, J
AB = 16.6), 4.72 (1 H, B of ABq, J
AB
= 16.6), 5.84 (d, 1 H, J = 3.9), 6.87 (s, 2 H), 6.88-6.96
(m, 2 H), 7.13≈7.35 (m, 8 H).
13C NMR (125 MHz CDCl
3) δ:
8.5, 12.3, 20.6, 22.7, 27.1,
47.9, 56.5, 77.7, 125.6, 126.8,
127.1, 127.5, 128.1 (2C), 131.9,
133.2, 138.4, 138.5, 139.9, 142.3,
172.2; IR (film from
CH
2Cl
2) cm
−1 : 2982, 1747,
1604, 1454, 1381, 1324, 1205,
1153, 1080, 1056, 1020, 859,
764, 730, 699, 659;
HRMS-FAB Calcd for C
28H
34NO
4S [M+H]+, 480.2209
m/
z; Found, 480.2186
m/
z; Anal. Calcd for C
28H
33NO
4S:
C, 70.12; H, 6.93; N, 2.92. Found: C, 70.40; H, 6.97; N, 2.90.
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
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