Hydrochloric Acid → 2-Naphthalenamine, 1,2,3,4-tetrahydro-5-methoxy-N-propyl-, hydrochloride (1:1), (2S)-

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Reaction Conditions

Reaction Steps

A 2 L reactor with double jacket temperature control was charged with 5-methoxy-2-aminotetraline hydrochloride (Xa) (161 g), sodium acetate (62 g), and tetrahydrofuran (750 mL). The suspension was stirred at 0° C. To that suspension were added glacial acetic acid (22 mL), sodium triacetoxyborohydride (200 g) and propionalhedyde (XIa) (48 g diluted with 50 mL of tetrahydrofuran via a dropping funnel maintaining the mass temperature below 10° C. The resulting suspension was stirred overnight at 0° C. To that suspension was slowly added a 25% solution of sodium hydroxide (250 mL) at 0° C. and the resulting mixture was let to warm up to room temperature under stirring for 30 minutes. The aqueous layer was discarded and the organic layer was washed with a 6.25% solution of sodium hydroxide (200 mL). The aqueous layer was discarded and the organic layer was heated at 50° C. To this solution concentrated hydrochloric acid (77 mL) was added over 20 minutes and the resulting thick suspension was diluted with 150 mL of tetrahydrofuran. The suspension is maintained at 50° C. for 30 minutes then rapidly cooled to 10° C. and stirred at 10° C. for 30 minutes. The product was isolated by filtration, washed 2 times with cold THF (2×200 mL) and dried under vacuum at 40° C. until constant weight to give N-Propyl MAT.HCl salt as an white solid with 78% yield.

Provenance & Evidence