Tris(1,1-dimethylethyl)phosphine → tert-Butyl 3-(7-amino-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

Temperatur

100 °C

Tris(dibenzylideneacetone)dipalladium(0) (0.056 g, 0.062 mmol) in THF (3 mL) was treated with tri-tert-butylphosphine 10% wt in hexanes (0.748 mL, 0.247 mmol) and was stirred vigorously under argon atmosphere for 10 minutes. tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate (0.49 g, 1.233 mmol) in THF (9 mL) and 1M LiHMDS in THF (3.70 mL, 3.70 mmol) were added to the mixture. The reaction was sealed, placed in a preheated oil bath, and refluxed at 100° C. The solution was cooled to room temperature, treated with 1M TBAF in THF (8 mL), and was stirred for 40 minutes. The mixture was concentrated and treated with 1N NaOH (50 mL). The mixture was transferred to a separatory funnel, diluted with water (50 mL), and extracted with EtOAc (2×50 mL). The organic phase was washed with brine (50 mL) and dried (Na2SO4). The crude material was subject to flash chromatography on silica gel (25-70% EtOAc/hexanes). The collected fractions were concentrated to give a clear brown oil (0.34 g, 83%). 1H NMR (CDCl3) δ 6.64 (d, J=8.7 Hz, 1H), 6.48 (s, 1H), 6.39 (brs, 1H), 4.08-4.02 (m, 1H), 3.70-3.07 (m, 6H), 3.09-3.07 (m, 2H), 2.08-1.92 (m, 2H), 1.46 (s, 9H); ESI-MS (m/z, %): 338, 336 (MH+, 40), 282, 280 (100).

1. customThe reaction was sealed
2. customplaced in a preheated oil bath
3. temperatureThe solution was cooled to room temperature
4. stirringwas stirred for 40 minutes
5. concentrationThe mixture was concentrated
6. additiontreated with 1N NaOH (50 mL)
7. customThe mixture was transferred to a separatory funnel
8. additiondiluted with water (50 mL)
9. extractionextracted with EtOAc (2×50 mL)
10. washThe organic phase was washed with brine (50 mL)
11. dry with materialdried (Na2SO4)
12. concentrationThe collected fractions were concentrated

ORD-Eintrag

ord-5ef0540213a64c93af7a56b8d8540a18

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08618286B2