Tetrahydrofuran → HCID 13324737, compound

Participants

Reaction Steps

A solution of 4.41 g (16.4 mmole) of α-(5-chloro-1-indolinyl)-m-tolunitrile of Example 17a in 30 ml distilled THF was added dropwise over 30 minutes to a rapidly stirred ice cold slurry of 2.49 g (65.6 mmole, 4.0 equivalents) LiAlH4 in 65 ml distilled THF under nitrogen. After warming to room temperature, the mixture was heated under reflux for 2.75 hours, cooled in an ice bath, and quenched by dropwise addition of 2.5 ml water, 2.5 ml 10% NaOH, and 7.5 ml water. The salts were filtered and washed with 250 ml boiling methylene chloride. The filtrate was concentrated and the residue was dissolved in methylene chloride (100 ml), washed with brine (250 ml), dried over K2CO3, and concentrated to give 4.29 g (95.9%) of crude free base. The free base (4.23 g, 15.5 mmole) was dissolved in 30 ml absolute ethanol and added to a warm solution of 1.80 g (15.5 mmole) fumaric acid in 80 ml absolute ethanol. The fumarate salt slowly crystallized upon cooling to room temperature, thus affording 5.12 g (84.9%) of 3-(5-chloro-1-indolinylmethyl)benzenemethanamine fumarate, m.p. 178° C., dec.

Provenance & Evidence