(S)-7-Bromo-1,2,3,4-tetrahydronaphthalen-1-amine synthesis

Yield:676135-98-1 86%

Reaction Conditions:

(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride at 20; for 12 h;

Steps:

102.B

B. Preparation of N- (lS, 2R)-11- (3, 5-Difluoro-benzyl)-3- [ (lS)-7- (2,2-dimethylpropyl)-1, 2,3, 4-tetrahydro-naphthalen-1-ylamino]-2- hydroxypropyl}-acetamide; The neopentyl zinc was prepared according to the procedure in Tetrahedron Letters, 1983, volume 24, page 3823-3824. To the bromotetralin amine (1 equiv, 8 mmol, 1.71 g) was added the crude neopentylzinc chloride suspension (3 equiv, 24 mmol, 48 mL), followed by Pd (dppf) Cl2-CH2Cl2 (0.05 equiv, 0.4 mmol, 330 mg). The reaction was stirred at ambient temperature under N2 (g) overnight. The suspension quickly turned yellow, and eventually turned purplish overnight. After 12 h, the reaction was quenched with NH4Cl (aq) and extracted 3x with EtOAc. The combined organic extracts were washed with brine and dried over Na2SO4, filtered and concentrated. Column chromatography on Si02 with 2 10 % MeOH in CH2Cl2 gave the desired neopentyl tetralin amine. (1. 5 g, 86% yield)

References:

WO2005/95326,2005,A2 Location in patent:Page/Page column 219-220