Triethylamine → HCID 53241112, compound

Temperature

0 °C

In a 2-necked round bottomed flask, bis(trichloromethyl)carbonate (174.5 mg, 0.59 mmol) was dissolved in DCM (10 mL). N,N-diethylethanamine (0.651 mL, 3.74 mmol) was added therein. The obtained solution was cooled to 0° C. In a separate vial, 4-[(5-amino-2-pyridinyl)oxy]-2-[(1-methylethyl)oxy]benzonitrile (Intermediate 156, 145.4 mg) was dissolved in DCM (10 mL). The obtained solution was added dropwise in 5 min to the chilled bis(trichloromethyl)carbonate solution. At the end of addition, at 0° C., having checked that 4-[(5-amino-2-pyridinyl)oxy]-2-[(1-methylethyl)oxy]benzonitrile completely disappeared, a solution in DCM (5 mL) of N,N-diethylethanamine (0.280 mL, 1.60 mmol) and (2R)-2-methyl-1-(methyloxy)-1-oxo-2-butanaminium chloride (Tetrahedron 1988, 44(15), 4793-6, 179.2 mg, 1.07 mmol) was added to the reaction mixture and it was stirred for 25 min. The reaction mixture was quenched with 10 mL of water, diluted with 50 mL of DCM, and acidified to pH˜5-6 using an aqueous pH 3 buffer solution. Phases were separated. The organic layer was washed with 15 mL of brine, dried over dry sodium sulphate, filtered and evaporated in vacuo to obtain a white foam. This foam was dissolved in 8 mL of methanol and Sodium methoxide (17.3 mg, 0.32 mmol) was added to the reaction mixture. The vial was sealed and shaken on PLS at 60° C. After 15 min, further sodium methoxide (17.3 mg, 0.32 mmol) was added portionwise to the reaction mixture and it was shaken up to 1.5 hr. The reaction mixture was then evaporated in vacuo using a biotage V10 apparatus to obtain a pale yellow solid. This crude was purified by Biotage SP1 (Silica; from 100:0 to 50:50 Cyclohexane/EtOAc in 10 CV) to give the title compound (116.5 mg).

1. additionAt the end of addition
2. customat 0° C.
3. customThe reaction mixture was quenched with 10 mL of water
4. additiondiluted with 50 mL of DCM
5. customPhases were separated
6. washThe organic layer was washed with 15 mL of brine
7. dry with materialdried over dry sodium sulphate
8. filtrationfiltered
9. customevaporated in vacuo
10. customto obtain a white foam
11. customThe vial was sealed
12. stirringshaken on PLS at 60° C
13. waitAfter 15 min
14. stirringwas shaken up to 1.5 hr
15. customThe reaction mixture was then evaporated in vacuo
16. customto obtain a pale yellow solid
17. customThis crude was purified by Biotage SP1 (Silica; from 100:0 to 50:50 Cyclohexane/EtOAc in 10 CV)

ORD record

ord-82b67668c1074d3da793cd359ab4f1de

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216967B2