Hexane → HCID 19426306, compound

Participants

Reaction Steps

A biphasic mixture of the bromohydrin (1.14 g, 5.0 mmol) in 2M aq. NaOH (100 mL) and CHCl3 (100 mL) was refluxed for 2.5 h. TLC (silica gel; 50% hexane-CH2Cl2) confirmed that formation of the epoxide was complete. The mixture was cooled to room temperature and the two layers were separated. The aq. phase was re-extracted with CHCl3 (2×30 mL) and discarded. The organic extracts were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield the crude epoxide as a pale yellow syrup which was redissolved in EtOH (30 mL) and Et3N (2 mL). Spiro[1H-indene-1,4'-piperidine] hydrochloride (1.11 g, 5.0 mmol) was added to this solution, and the resulting mixture was refluxed overnight. After 17 h, heating was stopped. The mixture was cooled to room temperature and concentrated to a residue in vacuo. The residue was dissolved in CH2Cl2 (50 mL) and the solution was washed with satd aq. NaHCO3 (30 mL). The aqueous extract was washed with CH2Cl2 (30 mL) and discarded. The organic extracts were combined, dried over anhydrous Na2SO4 and concentrated to a residue. The latter was dissolved in a minimum volume of CH2Cl2 and applied to a short column of silica gel which was subsequently eluted with 25% acetone-hexane. Concentration of the eluent yielded the product (0.91 g, 55%) as a brown syrup. The latter was estimated by tlc (silica gel, acetone(25):hexane (74):Et3N (1)) to be greater than 97% pure. The corresponding hydrochloride was prepared in MeOH as outlined for (11a) above, and recrystallized from isopropyl alcohol; mp 254°-257° C.; 1H NMR (CDCl3)δ1.46 (d, 2, piperidyl β-Heq., J= 12.8 Hz), 2.17 (m, 2, piperidyl β-Hax.), 2.86-3.49 (m, 8, tetrahydronaphthyl C1-H, C3-H, C4-H & piperidyl α-Hax.,eq.), 3.93-4.20 (m, 3, piperidyl α-Heq & CHOH), 6.79 (d, 1, indenyl C2-H, J=5.6 Hz), 6.90 (d, 1, indenyl C3-H, J=5.7 Hz), 7.03-7.42 (m, 8, aryl).

Provenance & Evidence