2-Methoxypropene → HCID 71230557, compound

Participants

Reaction Steps

Methyl 3-amino-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate (see WO 2008058393) (12.0 g, 50.6 mmol) in dichloromethane (150 mL) was placed in a cool water bath (12 deg C.) and treated dropwise with 2-methoxyprop-1-ene (14.6 mL, 152 mmol) over about 6 minutes followed by acetic acid (8.7 mL) over about 5 minutes. Sodium triacetoxyborohydride (16.1 g, 152 mmol) was added portionwise over about 30 minutes. The reaction mixture was allowed to warm to ambient temperature and was stirred for 16 h. The resulting light orange solution was poured into cold sodium bicarbonate (sat aq, 200 mL). The organic layer was separated and the aqueous layer was extracted twice with dichloromethane (150 mL each). The combined organic layers were washed with sodium bicarbonate (sat aq) and brine, dried over sodium sulfate (anhyd), filtered and concentrated to an orange oil. Silica gel chromatography (0-15% EtOAc:Hex) afforded 13.0 g (92% yield) of the desired methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)thiophene-2-carboxylate as a light yellow oil which solidified upon standing to a waxy crystalline solid, and was used in the subsequent step.

Provenance & Evidence