Hydrochloric Acid → HCID 59840696, compound

Participants

Reaction Steps

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.

Provenance & Evidence