Ethyl diazoacetate → HCID 178473104, compound

Participants

Reaction Steps

A suspension of trans (4-hydroxy-cyclohexyl)-carbamic acid tert-butyl ester (1.03 g, 4.80 mmol) in dry toluene (38 mL) under an nitrogen atmosphere was treated with rhodium acetate (110 mg, 200 μmol) and heated at reflux. A solution of ethyl diazoacetate (600 μL, 5.70 mmol) in dry toluene (9 mL) was added dropwise over 1.5 hours. The mixture was then stirred at reflux for a further 30 minutes and allowed to cool to ambient temperature overnight. The reaction was treated with a further portion of rhodium acetate (50 mg) and re-heated to reflux. Further ethyl diazoacetate (300 μL) in dry toluene (5 mL) was added dropwise over 1 hour. Heating was continued for 30 minutes and then the cooled mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel (gradient: 0-35% ethyl acetate in cyclohexane) to afford 720 mg (50%) of trans (4-tert-butoxycarbonylamino-cyclohexyloxy)-acetic acid ethyl ester as a white solid. LCMS (Method Q, ESI): RT=3.63 min, m+H=324.0; 1H NMR (400 MHz, CDCl3) δ: 4.35 (br s, 1H), 4.21 (q, 2H), 4.09 (s, 2H), 3.44 (br s, 1H), 3.32 (m, 1H), 2.04 (m, 4H), 1.44 (m, 11H), 1.28 (t, 3H), 1.13 (m, 2H).

Provenance & Evidence