Tetrahydrofuran → HCID 68292133, compound

Participants

Reaction Steps

To tert-butyl 8-benzyl-10-(1,2-dihydroxyethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.5 g, 3.69 mmol) in THF (35 mL) was added NaIO4 (2 g, 9.4 mmol) followed by the addition of H2O (13 mL). The reaction mixture was stirred at room temp for 2.5 hours. The reaction mixture was filtered, then concentrated in vacuo and the residue was partitioned between sat. aq. sodium bicarbonate (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted further with ethyl acetate (2×50 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated in vacuo. To the intermediate aldehyde (˜1.4 g) was added tBuOH (17 mL) and 2-methylbut-2-ene (10.5 mL, 99.04 mmol) and the reaction mixture was cooled to 0° C. A solution of NaClO2 (1.1 g, 9.65 mmol) and NaH2PO4 (1.33 g, 9.67 mmol) in water (17 mL) was added dropwise over 5 minutes, and the reaction mixture was stirred for 30 minutes at 0° C. The reaction mixture was warmed to room temperature, then extracted with ethyl acetate (4×50 mL) and the combined organics were dried over MgSO4, filtered and concentrated in vacuo to give the crude acid as a yellow oil. The oil was dissolved in toluene (2.5 mL) and methanol (2.5 mL), then diazomethyl(trimethyl)silane (1.85 mL of 2 M in hexanes, 3.69 mmol) was added dropwise until faint yellow color persisted. Acetic acid was added to make solution colorless (2 drops). The reaction mixture was concentrated in vacuo then purified by silica gel column chromatography using 0-70% EtOAc/hexane as eluent to give 9-tert-butyl 2-methyl 4-benzyl-1-oxa-4,9-diazaspiro[5.5]undecane-2,9-dicarboxylate (1 g, 67%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.37-7.20 (m, 5H), 4.43 (dd, J=10.5, 2.1 Hz, 1H), 3.74 (s, 3H), 3.57 (d, J=13.3 Hz, 3H), 3.45-3.29 (m, 2H), 3.14 (t, J=10.9 Hz, 1H), 3.08-3.01 (m, 1H), 2.56 (dd, J=11.3, 0.9 Hz, 1H), 2.30 (dd, J=8.7, 5.7 Hz, 1H), 2.13 (dd, J=19.9, 8.9 Hz, 1H), 1.91 (d, J=11.3 Hz, 1H), 1.69-1.46 (m, 3H), 1.43 (s, 9H). ESI-MS m/z calc. 404.5. found 405.7 (M+1)+; Retention time: 1.62 (3 min run).

Provenance & Evidence