Hydrochloric Acid → HCID 69059432, compound

Participants

Reaction Steps

To a solution of bicyclo[3.1.0]hexan-2-one (9.24 g, 96.1 mmol) and diethyl oxalate (14.7 g, 101 mmol) in EtOH (250 mL) at rt under N2 was added a solution of KOt-Bu in THF (106 mL of a 1M solution, 106 mmol). The reaction was stirred for 3.5 h at which time hydrazine hydrochloride (7.90 g, 115 mmol) in H2O (40 mL) was added. The reaction mixture was stirred for 20 h at rt and acidified to pH ˜3 by the addition of HCl (6N aq.). The volatiles were removed in vacuo and the resulting solid was diluted with EtOAc (500 mL) and H2O (500 mL). The layers were separated and the aqueous phase was back-extracted with EtOAc (300 mL). The combined organics were washed with brine (400 mL), dried over MgSO4, filtered, and concentrated to a crude oil that was determined to be approximately 75–80% pure (wt./wt.) ester by 1H NMR. The title compound was used directly in the next reaction (aminolysis) without further purification. 1H NMR (400 MHz, CDCl3): δ 10.55 (1H, bs), 4.32 (2H, q, J=6.8 Hz), 2.96 (1H, dd, J=16.8, 6.0 Hz), 2.80 (1H, d, J=17.2 Hz), 2.23–2.13 (2H, m), 1.35 (3H, t, J=7.2 Hz), 1.15 (1H, m), 0.34 (1H, m). 13C APT NMR (partial) (100 MHz, CDCl3): δ up: 127.4, 61.2, 26.8, 16.8; down: 23.0, 15.4, 14.5. HPLC/MS: Discovery® C18 column (5μ, 50×2.1 mm), 5% v/v CH3CN (containing 1% v/v TFA) in H2O (containing 1% v/v TFA) gradient to 99% v/v CH3CN in H2O, 0.75 mL/min, tr=1.62 min, ESI+=193.1 (M+H).

Provenance & Evidence