Ammonium Hydroxide → Methyl 1-(aminocarbonyl)-2-(3,4-dichlorophenyl)-2-(2-hydroxyethyl)cyclopropanecarboxylate

Tetrabutylammonium fluoride (TBAF) (5.6 mL, 1.1M/TFH) was added dropwise to a stirred solution of dimethyl 2-(3,4-dichlorophenyl)-2-(2-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}ethyl)-1,1-cyclopropanedicarboxylate (P14, 2.38 g) in THF (27 mL), at 0° C. After 4 h the ice-bath was removed and the reaction mixture was stirred for 3 h at RT. The solvent was removed under reduced pressure, the residue was treated with ether and water, the organic phase washed with brine, dried over Na2SO4 and the solvent evaporated under vacuum to give the crude lactone intermediate (2.08 g). This product was dissolved in a mixture of THF (15 mL) and methanol (10 mL), at RT, aqueous NH4OH (28%, 16 mL) was added dropwise and the reaction mixture was stirred for 4 h. The mixture was concentrated under reduced pressure, the residue was taken up with DCM and water, the organic phase was washed with brine, dried over Na2SO4 and the solvent evaporated under vacuum. The crude product was purified by FC (eluting with DCM/methanol from 1/0 to 9/1) to give the title compound (0.89 g) as a white foam.

1. customAfter 4 h the ice-bath was removed
2. customThe solvent was removed under reduced pressure
3. additionthe residue was treated with ether and water
4. washthe organic phase washed with brine
5. dry with materialdried over Na2SO4
6. customthe solvent evaporated under vacuum
7. customto give the crude lactone intermediate (2.08 g)
8. stirringthe reaction mixture was stirred for 4 h
9. concentrationThe mixture was concentrated under reduced pressure
10. washthe organic phase was washed with brine
11. dry with materialdried over Na2SO4
12. customthe solvent evaporated under vacuum
13. customThe crude product was purified by FC (eluting with DCM/methanol from 1/0 to 9/1)

ORD-Eintrag

ord-a5439c0126ab4ee98bc13cf853c988f5

Quelldatensatz

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07691893B2