Trimethylsilyl cyanide → 2-Amino-1-[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]ethanol

To a solution of 0.679 g of 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbaldehyde in 1.5 mL of CH2Cl2 was added ca. 5 mg of ZnI2, then 0.23 g of trimethylsilyl cyanide. The mixture was stirred at room temperature for 3 h, and then partitioned between 15 mL of water and 10 mL of Et2O. The aqueous phase was extracted with 2×10 mL of Et2O. The combined organics were dried over Na2SO4 and concentrated. The residue was dissolved in 15 mL of Et2O and cooled to 0° C. A 1-M solution of LiAlH4 in Et2O (4.2 mL) was added dropwise via addition funnel. The cooling bath was removed once the addition was complete, and the mixture was stirred overnight at room temperature, then recooled to 0° C. and quenched by dropwise addition of 0.15 mL of water, 0.15 mL of 15% aqueous NaOH, and 0.4 mL of water. The cooling bath was removed once the addition was complete, and the mixture was stirred 30 min at room temperature, filtered (washing the solids liberally with Et2O), and concentrated to provide the title compound, which was used without further purification. Mass spectrum (ESI) 354.2 (M+1). Some 1H NMR signals are doubled because of atropoisomerism. 1H NMR (500 MHz, CDCl3): δ 7.88 (s, 1H), 7.55 (app t, J=7.5 Hz, 1H), 7.22-7.28 (m, 2H), 6.99, 6.95 (d, J=2.5 Hz, 1H), 6.92, 6.90 (sm 1H), 4.52 (m, 1H), 3.70 (s, 3H), 2.90 (septet, J=7 Hz, 1H), 2.81 (m, 1H), 2.60-2.70 (m, 2H), 1.23-1.28 (m, 6H).

1. custompartitioned between 15 mL of water and 10 mL of Et2O
2. extractionThe aqueous phase was extracted with 2×10 mL of Et2O
3. dry with materialThe combined organics were dried over Na2SO4
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in 15 mL of Et2O
6. temperaturecooled to 0° C
7. additionA 1-M solution of LiAlH4 in Et2O (4.2 mL) was added dropwise via addition funnel
8. customThe cooling bath was removed once the addition
9. stirringthe mixture was stirred overnight at room temperature
10. customrecooled to 0° C.
11. customquenched by dropwise addition of 0.15 mL of water, 0.15 mL of 15% aqueous NaOH, and 0.4 mL of water
12. customThe cooling bath was removed once the addition
13. stirringthe mixture was stirred 30 min at room temperature
14. filtrationfiltered (
15. washwashing the solids liberally with Et2O), and
16. concentrationconcentrated

ORD record

ord-db053c419387441391f386469e54ca79

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2