Sodium Chloride → N-[(2R)-7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl]-(R)-3-chloromandelamide

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Reaction Steps

To a suspension of 2.6 g of (R)-2-amino-7-hydroxytetralin hydrochloride (PREPARATION II), 2.4 g of (R)-3-chloromandelic acid (Bull. Soc. Chim. Fr., 1973, 12, 3330) and 5.2 g of BOP in 60 ml of anhydrous methylene chloride, there is added 3.6 ml of triethylamine slowly, then the solution thus obtained is stirred at room temperature for 3 hours. After addition of 50 ml of a saturated sodium chloride solution, the reaction mixture is stirred for 30 minutes at room temperature, then 200 ml of ethyl acetate are added thereto and the phases are separated. The organic phase is washed twice with 30 ml of a 2N hydrochloric acid solution, then twice with 30 ml of a saturated sodium chloride solution. The organic solution is dried over sodium sulfate, filtered and evaporated to dryness. The oil thus obtained is purified by flash chromatography (eluent 55/45 mixture of ethyl acetate/cyclohexane). A doughy solid is obtained that is taken up with 20 ml of ethyl ether from which the product crystallizes. After addition of 10 ml of cyclohexane, the solution is filtered, washed with a 2/1 mixture of cyclohexane/ethyl ether and dried under reduced pressure at 50° C. to give 2.4 g (55%) of a stereoisomer that is pure according to 13C RMN at 60 MHz; m.p. 132°-134° C., [alpha]=+24.9° (methanol, c=1%). In TLC this product has the same shift of the product of Example 1(c), SR 58536 (RR,SS) and no impurity corresponding to the Rf of SR 58535 (RS,SR) of Example 1(b) (elution with 1/1 ethyl acetate/cyclohexane). After a further purification by chromatography, there is obtained the enantiomerically and chemically pure N-[(2R)-7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl]-(R)-3-chloromandelamide; m.p. 143°-147° C., [alpha]=+35.1° (methanol, c=1%). This product is identical with the compound SR 58533 of Example 8(c), the R,R configuration of which is thus confirmed.

Provenance & Evidence