V. P. Krasnov et al. / Tetrahedron: Asymmetry 15 (2004) 859–862
861
1
perature. All signals are expressed in ppm (d) with tetra-
methylsilane as an internal standard. Optical rotations
were measured on a Perkin–Elmer 241 polarimeter. The
de values of amides 6a, 7a and 8a were measured
by HPLC on a Merck–Hitachi chromatograph with
L-4000A Intelligent Pump, L-4000A UV Detector and
D-2500A Chromato-Integrator [Hibar Pre-packed Col-
umn RT250-4, Lichrosorb Si-60]; mobile phase: hexane–
i-PrOH ¼ 80:1, flow rate 1 mL/min; UV detection
C 72.38, H 5.84, N 8.05. H NMR (DMSO-d ): 1.02 (d,
-quinoline); 1.31 (dddd, J ¼ 13:2,
6
J ¼ 6:5 Hz, 3H, CH
3
3
10.2, 6.7, 5.3 Hz, 1H, C H-quinoline); 1.36 (d,
J ¼ 7:5 Hz, 3H, CH -alanine); 2.33 (dddd, J ¼ 13:2, 7.6,
3
3
5.4, 5.2 Hz, 1H, C H-quinoline); 2.49 (ddd, J ¼ 15:2,
4
10.2, 5.4 Hz, 1H, C H-quinoline); 2.68 (ddd, J ¼ 15:2,
4
5.3, 5.2 Hz, 1H, C H-quinoline); 4.60 (ddq, J ¼ 7:6, 6.7,
2
6.5 Hz, 1H, C H-quinoline); 5.48 (q, J ¼ 7:5 Hz, 1H, CH-
6
alanine); 7.21 (ddd, J ¼ 7:8, 6.8, 1.2 Hz, 1H, C H-quin-
5
7
2
30 nm; retention times s7a 16.3, s7b 14.0, s8a 16.0, s8b
7.3, s9a 17.6, s9b 17.1 min. Microanalyses were carried
out on a CHNS-O model EA-1102 elemental analyser
oline); 7.29 (m, 2H, C H- and C H-quinoline); 7.46 (d,
J ¼ 7:8 Hz, 1H, C H-quinoline); 7.84 (m, 4H, phthaloyl).
8
1
and were in good agreement with the calculated values.
0
4.5. N-[N -Phthaloyl-(2S)-alanyl]-(2RS)-2-methyl-
indoline 9a,b
4
.2. N-Phthaloyl-(S)-alanyl chloride 6
Following the above procedure, and starting with race-
mic 3 (0.49 g, 3.6 mmol) and N-phthaloyl-(S)-alanyl
chloride 6 (0.43 g, 1.8 mmol), the title compound was
obtained as colourless crystals (0.31 g, 51%). Anal.
Oxalyl chloride (1.75 mL, 20 mmol) and DMF (0.01 mL)
were added to a stirred solution of N-phthaloyl-(S)-
alanine (2.25 g, 10 mmol) in a hexane–benzene (1:1)
mixture (40 mL). The mixture was stirred at room tem-
perature for 20 h, then evaporated in vacuum to dryness.
The residue was treated with dry hexane to give com-
Calcd for C20
C 71.98, H 5.52, N 8.45. H NMR (DMSO-d ): 1.26 d
18 2 3
H N O : C 71.84, H 5.43, N 8.38. Found:
1
6
and 1.27 d (J ¼ 6:4 Hz, 3H, CH
3
-indoline); 1.69 d,
-alanine);
1
pound 6 as colourless crystals (2.22 g, 93%). H NMR
(
J ¼ 7:1 Hz and 1.81 d, J ¼ 7:3 Hz (3H, CH
3
3
CDCl
3
): 1.79 (d, J ¼ 7:1 Hz, 3H, CH
3
); 5.17 (q,
2.61 d, J ¼ 15:9 Hz and 2.64 d, J ¼ 15:8 Hz (1H, C H-
indoline); 3.26 dd, J ¼ 15:9, 8.6 Hz and 3.38 dd,
J ¼ 7:1 Hz, 1H, CH); 7.78 and 7.92 m (4H, C H ).
6
4
3
2
J ¼ 15:8, 8.3 Hz (1H, C H-indoline); 4.66 (m, 1H, C H-
indoline); 5.23 q, J ¼ 7:1 Hz and 5.25 q, J ¼ 7:3 Hz (1H,
CH-alanine); 6.95–7.88 (m, 8H, arom.).
0
.3. N-[N -Phthaloyl-(2S)-alanyl]-(3S)-2,3-dihydro-3-
methyl-4H-1,4-benzoxazine 7a
4
A solution of N-phthaloyl-(S)-alanyl chloride 6 (0.38 g,
1
4.6. (S)-2,3-Dihydro-3-methyl-4H-1,4-benzoxazine (S)-1
.6 mmol) in benzene (15 mL) was added dropwise to a
stirred solution of racemic 1 (0.48 g, 3.2 mmol) in ben-
zene (15 mL). The mixture was stirred at room temper-
ature for 20 h, then washed consequently with 1 M HCl,
Amide 7a (0.20 g, 0.58 mmol) was heated under reflux in
a mixture of glacial acetic acid (3 mL) and concd HCl
(3 mL) for 10 h. The reaction mixture was evaporated to
dryness. Water (5 mL) was added to the residue, the
precipitate filtered off and washed with water. The
combined aqueous filtrates were made alkaline with
10 M NaOH to pH 9–10 at +5 ꢁC and extracted
3 4
water, 5% NaHCO , water and dried over MgSO . The
solution was evaporated in vacuum to dryness to give a
yellow oily residue, which was recrystallised from hex-
ane–ethyl acetate yielding amide 7a as colourless crystals
2
0
(
1
5
(
1
1
1
1
0.25 g, 44%, de 99.8%). Mp: 204–206 ꢁC; ½aꢀ ¼ þ331 (c
with CHCl
3
(3 · 5 mL). The organic layer was washed
D
.3, benzene). Anal. Calcd for C H N O : C 68.56, H
.18, N 8.00. Found: C 68.43, H 5.13, N 8.09. H NMR
-benzoxazine);
with brine, and dried over MgSO . The solution was
evaporated to dryness to give amine (S)-1 as a yellowish
oil (0.08 g, 93%), ee 99.0% by HPLC (pre-column deri-
20
18
2
4
4
1
DMSO-d
6
): 1.15 (d, J ¼ 6:8 Hz, 3H, CH
3
1
20
D
.65 (d, J ¼ 7:4 Hz, 3H, CH -alanine); 4.08 (dd, J ¼
vatisation using (S)-naproxen chloride 4 ). ½aꢀ ¼ þ19:8
3
2
1
20
). {Lit. : (S)-1: ½aꢀ ¼ þ19:8 (c 1.0,
1:0, 3.2 Hz, 1H, C H-benzoxazine); 4.21 (dd, J ¼ 11:0,
(c 1.3, CHCl
3
D
2
.7 Hz, 1H, C H-benzoxazine); 4.71 (qdd, J ¼ 6:8, 3.2,
3 9
CHCl )}. Anal. Calcd for C H11NO: C 72.46, H 7.43, N
3
1
.7 Hz, 1H, C H-benzoxazine); 5.51 (q, J ¼ 7:4 Hz, 1H,
9.39. Found: C 72.42, H 7.35, N 9.37. H NMR
(DMSO-d ): 1.11 (d, J ¼ 6:3 Hz, 3H, Me), 3.39 (dqd,
6
8
CH-alanine); 6.91 (m, 2H, C H- and C H-benzoxazine);
6
7
3
7
7
(
.08 (ddd, J ¼ 8:1, 7.4, 1.6 Hz, 1H, C H-benzoxazine);
J ¼ 7:9, 6.3, 2.8 Hz, 1H, C H), 3.61 (dd, J ¼ 10:2,
5
2
2
.64 (dd, J ¼ 8:1, 1.6 Hz, 1H, C H-benzoxazine); 7.85
7.9 Hz, 1H, C H); 4.08 (dd, J ¼ 10:2, 2.8 Hz, 1H, C H);
5.46 (br s, 1H, NH), 6.41 (ddd, J ¼ 7:8, 7.1, 1.7 Hz, 1H,
m, 4H, phthaloyl).
6
5
C H), 6.50 (dd, J ¼ 7:8, 1.6 Hz, 1H, C H), 6.56 (dd,
8
J ¼ 7:6, 1.7 Hz, 1H, C H); 6.59 (ddd, J ¼ 7:6, 7.1,
0
7
4.4. N-[N -Phthaloyl-(2S)-alanyl]-(2S)-2-methyl-1,2,3,4-
tetrahydroquinoline 8a
1.6 Hz, 1H, C H).
Following the above procedure, and starting with race-
mic 2 (0.47 g, 3.2 mmol) and N-phthaloyl-(S)-alanyl
chloride 6 (0.38 g, 1.6 mmol), the title compound was
obtained as colourless crystals (0.30 g, 54%, de 99.7%).
4.7. (S)-2-Methyl-1,2,3,4-tetrahydroquinoline (S)-2
Following the above procedure, and starting with amide
8a (0.21 g, 0.6 mmol), the title compound was obtained
as a yellowish oil (0.085 g, 95%). Ee 99.0% by HPLC
(pre-column derivatisation using (S)-naproxen acyl
20
Mp: 230–231 ꢁC; ½aꢀ ¼ þ461 (c 1.45, benzene). Anal.
D
Calcd for C21
20 2 3
H N O : C 72.40, H 5.79, N 8.04. Found: