Hydrochloric Acid → HCID 57904819, compound

Participants

Reaction Steps

To a stirred solution of 8-(chloromethyl)-1,4-dioxaspiro[4.5]decane (78 g, 409 mmol) in THF (200 mL) was added 1N aq. HCl (500 mL, 500 mmol) at room temperature. After 24 h, 30% NH4OH (106 mL, 818 mmol) followed by NaCN (22.05 g, 450 mmol) were added and stirring continued for an additional 72 h at rt. The reaction mixture was then extracted with CH2Cl2 (5×100 mL). The combined CH2Cl2 extracts were treated with Na2CO3 (50.7 g, 409 mmol) in water (200 mL) followed by benzylchloroformate (58.4 mL, 409 mmol) at 0° C. and the resulting mixture allowed to warm to room temp and stirred overnight (16 h). After this, the reaction mixture was washed with sat. NaHCO3 (200 mL), then dried (Na2SO4), filtered and concentrated to afford a yellow residue. To this residue was added 20% ethyl acetate/hexane (150 mL) and the precipitated product was triturated with hexane (500 mL) and filtered. The filter cake was washed with hexane to afford benzyl 4-(chloromethyl)-1-cyanocyclohexylcarbamate (77 g, 251 mmol, 61% yield) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ: 7.31-7.40 (5 H, m), 5.14 (2 H, s), 4.92 (0.8 H, br.s.), 4.78 (0.2 H, br.s), 3.42 (2 H, dd, J=6.6, 2.3 Hz), 2.55-2.61 (2 H, m), 2.21-2.28 (1 H, m), 2.04 (2 H, s), 1.30-1.83 (4 H, m). LCMS (M+H) calcd for C16H20ClN2O2: 307.12; found: 307.07.

Provenance & Evidence