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Uses

tert-Butyl (S)-(1-([1,1'-Biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate may be useful in the preparation of tetrazolylalkylaminomethylphosphonates as neutral endopeptidase inhibitors.

Synthesis

GENERAL METHODS: (S)-2-(tert-butoxycarbonylamino)-3-(biphenyl-4-yl)propanoic acid (2.65 g, 10 mmol) was dissolved in tetrahydrofuran (20 mL) under nitrogen protection and the solution was cooled down to 0°C. Subsequently, triethylamine (1.42 mL, 1.1 eq.) was added to the solution and a white precipitate was observed to form.After 0.25 h, the reaction mixture was filtered. The filtrate was slowly added dropwise to a solution of sodium borohydride (0.62 g, 1.5 eq.) in water (8 mL) at 0 °C. After 0.5 h, the reaction mixture was gradually warmed up to room temperature and stirring was continued for 2 h. The reaction mixture was then stirred for 2 h. The solution was then mixed with 2M salt (1.5 mL, 1.1 eq.) and the reaction was completed with 2M salt. Upon completion of the reaction, the reaction mixture was acidified to pH=2 with 2 M hydrochloric acid and then extracted with ethyl acetate. The organic layer was subsequently washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate and concentrated under vacuum to afford the target product (S)-(1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamic acid tert-butyl ester (1.88 g, 75% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 1208 - 1212