Sodium Chloride → HCID 11014455, compound

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Reaction Steps

The product so obtained may be used for the preparation of N-[(2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(2R)-2-hydroxy-2-phenylethanamine (R,S isomer of COMPOUND 1) as follows: (a) To a suspension of 5.7 g of (S)-2-amino-7-carbethoxymethoxytetraline hydrochloride, 3 g of (R)-mandelic acid and 8 g of benzotriazolyl-N-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) in 100 ml of anhydrous methylene chloride, there is slowly added 5.6 ml of triethylamine, then the solution thus obtained is left under stirring at room temperature for 5 hours. After addition of 150 ml of a saturated solution of sodium chloride, the mixture is left under stirring for 30 minutes at room temperature, added with 500 ml of ethyl acetate. The organic phase is washed at first with a 1N solution of hydrochloric acid, then with a saturated solution of sodium bicarbonate and sodium chloride. The organic solution is dried on sodium sulfate, filtered and evaporated to dryness. The oil thus obtained is purified by flash chromatography by using a mixture of ethyl acetate/cyclohexane 55/45 as a solvent. The resulting solid is triturated in 20 ml of ethyl ether and the product thus obtained is crystallized from ethyl acetate to give N-[(2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(R)-mandelamide; m.p. 115°-117° C.; /alpha/=-98.3° (methanol, c=1%). Yield: 55%. (b) To a solution of 5 g of N-[(2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(R)-mandelamide in 50 ml of anhydrous tetrahydrofuran, 2.6 ml of a 10M solution of boranemethylsulfide (diborane generating reagent consisting of a complex of borane and dimethylsulfide) in 10 ml of anhydrous tetrahydrofuran are added drop by drop during 10 minutes under nitrogen at a temperature of 0° C. The mixture is left to stand overnight at room temperature. The unreacted borane-methylsulfide is destroyed by cautiously adding 30 ml of absolute ethanol and heating at reflux for 30 minutes. After evaporation to dryness a flash chromatography is carried out by eluting with a mixture of ethyl acetate/methanol 85/15 . Two products separate which are taken up with ethyl ether. The less polar product gives, after crystallization from ethyl acetate, 1.2 g of N-[(2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(2R)-2-hydroxy-2-phenylethanamine; m.p. 108°-111° C.; /alpha/=-78.65° (methanol, c=1%). The more polar product gives, after crystallization from ethyl acetate, 0.5 g of N-[(2S)-7-(2-hydroxyethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(2R)-2-hydroxy-2-phenylethanamine; m.p. 94°-96° C.; /alpha/=-83.68° (methanol, c=1%).

Provenance & Evidence