Picolinic acid → (S,S)-DACH-pyridyl Trost ligand

Temperature

18.5 °C

A 22 L flask was charged with 1,1′-carbonyldimidazole (1.7 Kg, 10.48 mol) and THF (7.5 L). Solid picolinic acid (1.36 Kg, 11 mol) was added to the slurry at room temperature. The reaction was endothermic causing the mixture to cool from 18° C. to 12° C. The reaction mixture was then warmed to 18-19° C. The resulting clear solution was stirred for 1 h and molten (1S,2S)-(+)-1,2-diaminocyclohexane (0.5 Kg, 4.38 mol) was added while keeping the temperature below 50° C. The beaker and funnel were rinsed with 2.5 L of THF. The reaction was stirred at rt for 15 h. Water (0.5 L) was added to the thin slurry giving a clear solution and the reaction mixture was stirred for 1 h. The reaction mixture was concentrated to an orange semi-solid by rotary evaporation. The reaction product was slurried in 5 L of ethanol and concentrated by rotary evaporation. The reaction product was dissolved in ethanol (5 L) at 64-65° C. The solution was allowed to cool. The solution turned hazy around 58° C. At this temperature, the hazy solution was seeded (10 g) and cooled to −8° C. The resulting white crystals were isolated by filtration on a sintered glass funnel, washed with 5 L of cold ethanol (−8 to −10° C.), dried under house vacuum with nitrogen sweep, and then dried in a vacuum oven (35° C.). This resulted in the isolation of 1.23 Kg (86.3%) of white crystalline solid.

1. temperatureto cool from 18° C. to 12° C
2. customthe temperature below 50° C
3. washThe beaker and funnel were rinsed with 2.5 L of THF
4. stirringThe reaction was stirred at rt for 15 h
5. additionWater (0.5 L) was added to the thin slurry
6. customgiving a clear solution
7. stirringthe reaction mixture was stirred for 1 h
8. concentrationThe reaction mixture was concentrated to an orange semi-solid by rotary evaporation
9. concentrationconcentrated by rotary evaporation
10. dissolutionThe reaction product was dissolved in ethanol (5 L) at 64-65° C
11. temperatureto cool
12. customturned hazy around 58° C
13. temperaturecooled to −8° C
14. customThe resulting white crystals were isolated by filtration on a sintered glass funnel
15. washwashed with 5 L of cold ethanol (−8 to −10° C.)
16. customdried under house vacuum with nitrogen sweep
17. customdried in a vacuum oven (35° C.)

ORD record

ord-236d39750575456dac7b784cf770896f

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06358979B1