Triethylamine → (1-Azido-3-methyl-1-butyl)(3 buten-1-yl)methylphenylsilane

To a solution of 46 (3.4 g, 13 mmol) in CH2Cl2 (150 mL) and Et3N (9 mL, 65 mmol) at 0° C. was added dropwise over 5 min methanesulfonyl chloride (7.4 g, 65 mmol), and the mixture was allowed to warm to rt over 1 h. After stirring overnight under argon, the mixture was cooled to 0° C. and quenched with water (50 mL). The organic layer was isolated and the aqueous layer extracted twice with 50-mL portions of CH2Cl2. The combined organic extracts were concentrated in vacuo at rt. The crude mesylate was dissolved in DMF (150 mL), and to this solution was added sodium azide (4.2 g, 64.8 mmol). After stirring overnight at rt, the mixture was partitioned between water (200 mL) and EtOAc (200 mL). The organic layer was isolated and the aqueous layer extracted twice with 50-mL portions of EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated. Flash chromatography over silica gel (1/19 EtOAc:hexane) gave a colorless oil of pure 47 as a mixture of diastereomers (3.11 g, 84%): Rf=0.80 (1/9 EtOAc:hexane); 1H NMR (300 MHz, CDCl3) δ 7.53-7.47 (m, 2H), 7.38-7.32 (m, 3H), 5.91-5.78 (m, 1H), 5.0-4.86 (m, 2H), 3.03 and 2.99 (two triplets due to diastereomers, J=2.7 Hz, 1H), 2.08 (q, J=7.8 Hz, 2H), 1.82-1.70 (m, 1H), 1.58-1.47 (m, 1H), 1.19-1.10 (m, 1H), 1.06-0.94 (m, 2H), 0.89-0.83 (m, 6H), 0.38 and 0.36 (two singlets due to diastereomers, 3H); 13C NMR (75 MHz, CDCl3) δ 140.8, 134.2, 134.1, 129.6, 128.0, 113.3, 50.4, 50.3, 38.6, 38.5, 27.5, 25.8, 23.3, 20.7, 11.4, 11.0, −6.8, −7.3; IR (neat) 3067 (w), 2956 (s), 2914 (m), 2865 (m), 2099 (s), 1640 (m), 1469 (w), 1427 (m), 1259 (s), 1113 (m), 999 (w), 909 (m), 795 (m), 738 (m), 699 (m) cm−1; MS (FAB) m/e (rel. intensity) 288 (MH+, 19), 262 (10), 261 (32), 260 (100), 259 (29), 258 (39), 253 (14), 245 (20), 244 (64), 233 (15), 217 (11), 216 (16), 207 (19), 204 (54); HRMS (FAB) calcd for C16H26N3Si: 288.1896, found: 288.1895.

1. temperaturethe mixture was cooled to 0° C.
2. customquenched with water (50 mL)
3. customThe organic layer was isolated
4. extractionthe aqueous layer extracted twice with 50-mL portions of CH2Cl2
5. concentrationThe combined organic extracts were concentrated in vacuo at rt
6. dissolutionThe crude mesylate was dissolved in DMF (150 mL)
7. stirringAfter stirring overnight at rt
8. customthe mixture was partitioned between water (200 mL) and EtOAc (200 mL)
9. customThe organic layer was isolated
10. extractionthe aqueous layer extracted twice with 50-mL portions of EtOAc
11. washThe combined organic extracts were washed with saturated aqueous NaCl
12. dry with materialdried over Na2SO4
13. concentrationconcentrated
14. customFlash chromatography over silica gel (1/19 EtOAc:hexane) gave a colorless oil of pure 47
15. additionas a mixture of diastereomers (3.11 g, 84%)

ORD-Eintrag

ord-10bb8e52b1f84cd9ae72693ba9d90473

Quelldatensatz

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06441212B1