(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine → tert-Butyl 6-[(2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl]hexanoate

To a stirred solution of (2R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.0 eq.) in THF at −78° C., was added dropwise over 10 min a solution of BuLi (1.6 N in hexane, 1.0 eq.) and stirring was continued at −78° C. for 45 min. A pre-cooled solution of tert-butyl 6-iodohexanoate (1.0 eq.) in THF was then added by cannula over 5 min and the reaction stirred overnight, slowly warming to RT. The reaction was then left to stir at RT for a further hour and was quenched by the addition of aqueous NH4Cl solution. The THF layer was decanted off and concentrated under reduced pressure, meanwhile and the aqueous mixture was extracted with EtOAc (3×). The EtOAc extracts were used to redissolve the oily THF residue and this solution was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude was used directly in the next step without further purification (I1).

1. stirringthe reaction stirred overnight
2. waitThe reaction was then left
3. stirringto stir at RT for a further hour
4. customwas quenched by the addition of aqueous NH4Cl solution
5. customThe THF layer was decanted off
6. concentrationconcentrated under reduced pressure
7. extractionmeanwhile and the aqueous mixture was extracted with EtOAc (3×)
8. dissolutionto redissolve the oily THF residue
9. washthis solution was washed with brine
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated under reduced pressure
12. customThe crude was used directly in the next step without further purification (I1)

ORD-Eintrag

ord-2c34b75b684e4155920777c7fd1c69d2

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07863294B2