Lithium Chloride → Tert-butyl 2-[3-(2,2-dimethylpropionylamino)-2-methoxycarbonylphenylethynyl]-pyrrolidine-1-carboxylate

HRID 715972

Reaction equation

HRID 715972 reaction equation
[CH3:1][C:2]([CH3:25])([CH3:24])[C:3]([NH:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12](OS(C(F)(F)F)(=O)=O)[C:7]=1[C:8]([O:10][CH3:11])=[O:9])=[O:4].C([Sn](CCCC)(CCCC)[C:31]#[C:32][CH:33]1[CH2:37][CH2:36][CH2:35][N:34]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])CCC.[Cl-].[Li+]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][C:2]([CH3:25])([CH3:24])[C:3]([NH:5][C:6]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:12]([C:31]#[C:32][CH:33]2[CH2:37][CH2:36][CH2:35][N:34]2[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:13]=[CH:14][CH:15]=1)=[O:4]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 70984584Tert-butyl 2-tributylstannanylethynylpyrrolidine-1-carboxylate2×HCID 86712118Methyl 2-(2,2-dimethylpropionylamino)-6-trifluoromethanesulfonyloxybenzoate2×

Product 1

HCID 70982938Tert-butyl 2-[3-(2,2-dimethylpropionylamino)-2-methoxycarbonylphenylethynyl]-pyrrolidine-1-carboxylateYield 86.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of methyl 2-(2,2-dimethylpropionylamino)-6-trifluoromethanesulfonyloxybenzoate (Intermediate 39, 3.83 g), tert-butyl 2-tributylstannanylethynyl-pyrrolidine-1-carboxylate (Intermediate 41, 5.81 g), bis(triphenylphosphine)palladium(II) dichloride (0.702 g) and lithium chloride (1.28 g) in dimethylformamide (50 mL) was stirred and heated at 95° C. under nitrogen for 1 hour. After cooling, the mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give tert-butyl 2-[3-(2,2-dimethylpropionylamino)-2-methoxycarbonyl-phenylethynyl]-pyrrolidine-1-carboxylate (3.71 g) as a viscous gum.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated in vacuo
  3. customthe residue was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%

Sources & evidence

ORD record
ord-a95fe76c005a4de5852ca2e20558e15c
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Linked notes

Loading…