Reacción #1998189

Ecuación de reacción

sodium azide

trans-1,2-bis(methylamino)cyclohexane

L-ascorbic acid sodium salt

tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate

→

tert-butyl rel-((4aS,10bS)-9-azido-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate

Rendimiento 70.0%

Disolventes

water

water

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe mixture was purged with nitrogen for 10 min
2. 2
   Extracciónwas extracted three times with ethyl acetate
3. 3
   LavadoThe combined organic layers were washed with brine
4. 4
   Secadodried over sodium sulfate
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   OtroThe crude product was purified

Procedimiento

To a solution of tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate from preparation C (300 mg, 0.729 mmol) in ethanol (3.6 mL) was added sodium azide (228 mg, 3.51 mmol), trans-1,2-bis(methylamino)cyclohexane (55 mg, 0.387 mmol), 0.66 M solution of aqueous L-ascorbic acid sodium salt (0.780 mL, 0.515 mmol) and water (0.70 mL) and the mixture was purged with nitrogen for 10 min. A 0.33 M solution of aqueous copper(II) sulfate pentahydrate (0.780 mL, 0.257 mmol) was added and the reaction was heated to 80° C. for 12 min. The reaction was poured into water and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using silica gel column chromatography (2:1 hexanes/EtOAc) to afford tert-butyl rel-((4aS,10bS)-9-azido-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate (190 mg, 0.509 mmol, 70% yield) as a clear viscous oil. LCMS (M+Na)+=396.1. 1H NMR (500 MHz, chloroform-d) δ 7.11 (br. s., 1H), 7.09 (d, J=8.2 Hz, 1H), 6.89 (dd, J=8.2, 2.1 Hz, 1H), 3.03 (dd, J=12.9, 3.6 Hz, 1H), 2.94-2.79 (m, 3H), 2.27 (br. s., 1H), 2.21-2.07 (m, 1H), 1.99 (dq, J=13.8, 6.7 Hz, 1H), 1.62 (s, 3H), 1.48 (s, 9H).

Fuente