4454
H. Bernsmann et al. / Tetrahedron 58 /2002) 4451±4457
70 eV) m/z 9relative intensity): 241 90.5) [M12N2], 226 94)
[M12C3H7 or M12HN3], 210 910) [M12CO2CH3], 198
923) [M12C3H72N2], 182 95) [M12CH3CHCO2CH3],
171 96) [M12C4H8N3], 157939) [M 12C5H10N3], 112
934) [C5H10N31], 88 977) [C4H8O21], 43 965) [C3H71], 41
9100); Anal. calcd for C13H23N3O3: C, 57.97; H, 8.61; N,
15.60. Found C, 58.00; H, 8.68; N, 15.48.
®lter funnel G5, and the ®ltrate was evaporated in vacuo to
give the amino acid 6a 9156 mg, 83%). Similarly, 6b
9253 mg, 79%) was obtained from 5b 9356 mg,
1.39 mmol) after puri®cation by ¯ash chromatography
9methanol).
4.5.1. Amino acid 6a. Colorless solid; mp 185±1888C
9decomposition); IR 9KBr): 3200±2500 9br, s, OH), 2970
9s), 2918 9s), 2877 9s), 2568 9m), 2224 9m), 1629 9s, CvO),
1552 9s), 15479s), 1460 9m), 1406 9s), 1362 9m), 1103 9m),
1074 9m), 1060 9m) cm21; 1H NMR 9CD3OD, 300 MHz): d
1.10 9d, J7.0 Hz, 3H), 1.32 9d, J6.8 Hz, 3H), 1.56±2.07
9m, 6H), 2.23 9dq, Jd7.0 Hz, Jq7.0 Hz, 1H), 3.48±3.58
9m, 1H), 3.86±3.93 9m, 1H), 4.06±4.11 9m, 1H); 13C NMR
9CD3OD, 75.5 MHz): d 16.50 9q), 19.58 9q), 30.82 9t), 32.06
9t), 39.76 9t), 47.20 9d), 50.65 9d), 77.50 9d), 84.78 9d),
184.28 9s); MS 9ESI) m/z: 224.1 [M1Na1], 202.1
[M1H1], 184 [M1H12H2O]; Anal. calcd for
C10H19NO3: C, 59.68; H, 9.52; N, 6.96. Found C, 59.56;
H, 9.87; N, 6.95.
4.4. Preparation of azido acids 5
To a solution of azido ester 4a 91.21 g, 5.0 mmol) in MeOH
920 mL) was added 2N NaOH 920 mL, 40.0 mmol) at room
temperature, and the mixture was stirred vigorously for
10 h. The mixture was acidi®ed to pH 1 with 2N HCl,
extracted with ethyl acetate 94£15 mL), and the combined
organic layers were dried over MgSO4. Concentration in
vacuo and puri®cation of the residue by ¯ash chromato-
graphy 9dichloromethane/ether 4:1) gave azido acid 5a
91.04 g, 92%). Similarly, 5b 9861 mg, 90%) was obtained
from 4b 91.01 g, 3.75 mmol).
4.5.2. Amino acid 6b. White needles; Rf 0.44 9methanol);
mp 2498C 9decomposition); IR 9KBr): 3419 9m), 2963 9s),
2936 9s), 2874 9s), 2364 9m), 2146 9w), 1567 9s, CvO),
1461 9m), 1402 9s), 1365 9m), 12879w), 1090 9w), 1062
4.4.1. Azido acid 5a. Colorless oil; Rf 0.27±0.54 9dichloro-
methane/ether 1:1); IR 9neat): 3500±2500 9br, m, OH), 2966
9s), 2945 9s), 2109 9s, N3), 1715 9s, CvO), 1455 9s), 1419
1
9s), 1377 9s), 1251 9s), 1089 9s), 1061 9s) cm21; H NMR
9m) cm21
;
1H NMR 9CD3OD, 500 MHz): d 1.05 9t,
9CDCl3, 300 MHz): d 1.179d, J7.1 Hz, 3H), 1.29 9d,
J6.5 Hz, 3H), 1.42±1.72 9m, 4H), 1.97±2.11 9m, 2H),
2.51 9dq, Jd7.1 Hz, Jq7.1 Hz, 1H), 3.61±3.72 9m, 1H),
4.01±4.09 9m, 2H); 13C NMR 9CDCl3, 75.5 MHz): d 13.30
9q), 20.04 9q), 28.71 9t), 31.16 9t), 42.85 9t), 45.26 9d), 55.54
9d), 76.62 9d), 80.35 9d), 179.63 9s); MS 9GC/MS, 70 eV)
m/z 9relative intensity): 184 93) [M12HN3], 154 913)
[M12CH3CHCO2H], 143 917) [M12C3H6N3], 125 940)
[M12C3H6N32H2O], 84 923) [C3H6N31], 70 924)
[C2H4N31], 42 9100); Anal. calcd for C10H17N3O3: C,
52.85; H, 7.54; N, 18.49. Found C, 53.11; H, 7.66; N, 18.55.
J7.3 Hz, 3H), 1.17 9d, J7.1 Hz, 3H), 1.45±1.53 9m,
2H), 1.64±1.80 9m, 4H), 1.90 9ddd, J3.4, 7.2, 15.3 Hz,
1H), 1.98 9ddd, J2.9, 7.9, 15.3 Hz, 1H), 2.02±2.12 9m,
2H), 2.36 9dq, Jd7.1 Hz, Jq7.1 Hz, 1H), 3.43 9ddd,
J2.9, 7.1, 7.1 Hz, 1H), 3.96 9ddd, J7.2, 7.2, 7.2 Hz,
1H), 4.12±4.179m, 1H); 13C NMR 9CD3OD, 126 MHz): d
14.879q), 16.56 9q), 20.60 9t), 30.82 9t), 32.179t), 36.379t),
37.49 9t), 50.88 9d), 51.14 9d), 77.46 9d), 84.89 9d), 184.48
9s); MS 9EI, 70 eV) m/z 9relative intensity): 186 931)
[M12C3H7], 15791) [M 12C4H8NH2], 143 942)
[M12C5H10NH2], 86 94) [C5H10NH21], 72 9100)
[C4H8NH21]; HRMS 9EI, 70 eV) Calcd for C12H23NO3
[M1]: 229.168. Found: 229.164.
4.4.2. Azido acid 5b. White needles; Rf 0.30±0.48
9dichloromethane/ether 4:1); mp 34±398C; IR 9KBr): 3029
9br, m, OH), 2962 9s), 2939 9s), 2876 9s), 2102 9s, N3), 1737
9s, CvO), 1712 9s, CvO), 1465 9m), 1276 9s), 1259 9s),
4.6. Preparation of amino esters 7
1
1228 9s), 1066 9s) cm21; H NMR 9CDCl3, 500 MHz): d
0.93 9t, J7.1 Hz, 3H), 1.15 9d, J7.0 Hz, 3H), 1.37±1.68
9m, 8H), 2.00±2.08 9m, 2H), 2.51 9dq, Jd7.5 Hz,
Jq7.5 Hz, 1H), 3.47±3.50 9m, 1H), 4.01±4.08 9m, 2H);
13C NMR 9CDCl3, 126 MHz): d 13.92 9q), 13.82 9q),
19.19 9t), 28.81 9t), 31.21 9t), 37.13 9t), 41.04 9t), 45.22
9d), 60.18 9d), 76.75 9d), 80.30 9d), 179.32 9s); MS
9GC/MS, 70 eV) m/z 9relative intensity): 212 91)
[M12C3H7 or M12HN3], 184 911) [M12C3H72N2], 143
928) [M12C5H10N3], 125 957) [M12C5H10N32H2O], 112
922) [C5H10N31], 98 913) [C4H8N31], 69 972) [C5H91], 43
997) [C3H71], 41 9100); Anal. calcd for C12H21N3O3: C,
56.45; H, 8.29; N, 16.46. Found C, 56.57; H, 8.57; N, 16.80.
To a solution of azido ester 4a 91.61 g, 6.67mmol) in
MeOH 940 mL) was added 10% Pd/C 9160 mg) at ambient
temperature. After purging the suspension with hydrogen
95 min), stirring was continued for 12 h 94a) or 24 h 94b)
under a hydrogen atmosphere of 10 bar 94a) or 1.5 bar 94b).
The catalyst was removed by ®ltration through a glass ®lter
funnel G5, and the ®ltrate was evaporated in vacuo to give
the amino ester 7a 91.40 g, 98%). Similarly, 7b 9447mg,
96%) was obtained from 4b 9515 mg, 1.91 mmol).
4.6.1. Amino ester 7a. Colorless oil; IR 9neat): 3311 9w,
NH), 3302 9w, NH), 2955 9s), 2877 9s), 1740 9s, CvO),
1596 9w), 1460 9m), 1436 9m), 1377 9m), 1263 9m), 1199
1
4.5. Preparation of amino acids 6
9s), 1164 9s), 1085 9s), 1063 9s) cm21; H NMR 9CDCl3,
300 MHz): d 1.079d, J6.4 Hz, 3H), 1.10 9d, J7.0 Hz,
3H), 1.39±1.63 9m, 6H), 1.89±2.03 9m, 2H), 2.51 9dq,
Jd7.0 Hz, Jq7.0 Hz, 1H), 3.01±3.12 9m, 1H), 3.67 9s,
3H), 3.92±4.02 9m, 3H); 13C NMR 9CDCl3, 75.5 MHz): d
13.40 9q), 24.31 9q), 28.52 9t), 31.32 9t), 44.34 9d), 45.42 9d),
45.61 9t), 51.59 9q), 76.91 9d), 80.53 9d), 175.38 9s); MS
9ESI) m/z: 238 [M1Na1], 216 [M11H1]; Anal. calcd for
To a solution of azido acid 5a 9210 mg, 0.93 mmol) in dry
MeOH 930 mL) was added 10% Pd/C 930 mg) at ambient
temperature. After purging the suspension with hydrogen
95 min), stirring was continued for 10 h 95a) or 1 h 95b)
under a hydrogen atmosphere of 10 bar 95a) or 1.5 bar
95b). The catalyst was removed by ®ltration through a glass-