Hydrochloric Acid → HCID 59840696, compound

To a stirred solution of 3-(azidomethyl)-2-methyl-6-(trifluoromethyl)pyridine (292 mg, 1.35 mmol) in tetrahydrofuran (5 mL) was added triphenylphosphine (710 mg, 2.7 mmol), and the mixture was stirred to dissolution. After 5 min the mixture was placed in an oil bath at 50° C. and stirred overnight. The mixture was hydrolyzed with 2M HCl (3 μL) for 0.5 h, then partitioned between ethyl acetate (30 mL) and 0.5 M NaH2PO4 (30 mL). The organic phase was extracted with 0.5 M NaH2PO4 (10 mL), and the combined acidic aqueous extracts were basified with 50% KOH, and extracted with CH2Cl2 (2×30 mL). The combined CH2Cl2 layers were dried (Na2SO4), filtered and concentrated to a faintly yellow semi-solid (0.53 g). NMR and LC-MS showed that the material was only partially cleaved to the free amine (40%) with the remaining 60% being the phospinimine. The mixture was dissolved in MeOH (10 mL) and heated at reflux for 2 h. The mixture was concentrated in vacuo and the residue was treated with water (10 mL) and 6N HCl to pH<1, and ether (20 mL). The aqueous phase was separated and extracted with ether (20 mL). The aqueous layer was adjusted to pH>13 with 2N aq. KOH and extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to yield an oil which was used for the next step reaction without further purification.

1. stirringstirred overnight
2. custompartitioned between ethyl acetate (30 mL) and 0.5 M NaH2PO4 (30 mL)
3. extractionThe organic phase was extracted with 0.5 M NaH2PO4 (10 mL)
4. extractionextracted with CH2Cl2 (2×30 mL)
5. dry with materialThe combined CH2Cl2 layers were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated to a faintly yellow semi-solid (0.53 g)
8. dissolutionThe mixture was dissolved in MeOH (10 mL)
9. temperatureheated
10. temperatureat reflux for 2 h
11. concentrationThe mixture was concentrated in vacuo
12. additionthe residue was treated with water (10 mL) and 6N HCl to pH<1, and ether (20 mL)
13. customThe aqueous phase was separated
14. extractionextracted with ether (20 mL)
15. extractionextracted with CH2Cl2 (3×50 mL)
16. washThe combined organic layers were washed with brine
17. dry with materialdried (Na2SO4)
18. concentrationconcentrated
19. customto yield an oil which
20. customwas used for the next step reaction without further purification

ORD record

ord-1c1ac0da05d24998a17b902302af30aa

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076345B2