Piperidine → HCID 59226716, compound

Participants

Reaction Steps

A mixture of 5-methylsulfanyl-thiophene-2-carbaldehyde (1.0 g, 6.3 mmol) and 3-amino-propionic acid tert-butyl ester hydrochloride (1.02 g, 7 mmol) in DCM (20 mL) was stirred at RT for 15 min. Sodium triacetoxyborohydride (2 g, 9.45 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mass was partitioned between aqueous sodium bicarbonate and DCM. The organic layer was dried over sodium sulfate and concentrated to give the crude 3-[(5-methylsulfanyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl ester (800 mg, 38% yield). This crude amine (800 mg, 2.4 mmol) was dissolved in DCM (10 mL) and Fmoc-isothiocyanate (740 mg, 2.6 mmol) was added. After stirring the reaction overnight at room temperature, piperidine (3 mL) was added and the deprotection reaction was stirred for 30 min. The reaction mixture was concentrated and purified using a silica gel column. Concentration of the appropriate fractions under vacuum gave the desired thiourea (600 mg, 63% yield). This material is unstable and should be kept in the cold to prevent decomposition by cyclization and loss of t-BuOH. LC-MS m/z: 347 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 6.85 (d, 1H), 6.82 (d, 1H), 5.85 (s, 2H), 3.52 (t, 2H), 2.65 (t, 2H), 2.41 (s, 3H), 2.38 (s, 3H), 1.38 (s, 9H).

Provenance & Evidence