Potassium Phosphate, Tribasic → tert-Butyl 1-(3-amino-4-cyclopropylbenzyl)cyclopropanecarboxylate

HRID 1475676Notes

Reaction equation

HRID 1475676 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1Cl)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1CCCCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[CH:20]1[CH2:22][CH2:21]1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806Tricyclohexylphosphine2×HCID 2760897Cyclopropylboronic acidHCID 67957815tert-Butyl 1-(3-amino-4-chlorobenzyl)cyclopropanecarboxylate

Product 1

HCID 68009453tert-Butyl 1-(3-amino-4-cyclopropylbenzyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolventHCID 21867204Cyclohexane ethylacetateSolvent

Conditions

Temperature
150 °C

Procedure

200 mg (0.71 mmol) of tert-butyl 1-(3-amino-4-chlorobenzyl)cyclopropanecarboxylate were dissolved in 6 ml of dioxane, the mixture was inertized with argon and 122 mg (1.42 mmol) of cyclopropylboronic acid, 256 mg (1.21 mmol) of potassium phosphate, 5 mg (0.02 mmol) of tricyclohexylphosphine and 6.5 mg (0.007 mmol) of tris(dibenzylideneacetone)dipalladium were added. The reaction mixture was then stirred in a microwave apparatus (Biotage) at a target temperature of 150° C. for 1 h. The reaction was checked by TLC (mobile phase cyclohexane/ethyl acetate 4:1), after which a further 10 mg of tricyclohexylphosphine and 13 mg of tris(dibenzylideneacetone)dipalladium were metered in, and the reaction mixture was stirred at 150° C. for another 2 h. The mixture was then filtered through kieselguhr, the residue was washed with dioxane and the combined filtrate was concentrated to dryness. The residue obtained was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gave 120 mg (59% of theory) of the target compound.

Workup

  1. additionwere added
  2. stirringwas stirred at 150° C. for another 2 h
  3. filtrationThe mixture was then filtered through kieselguhr
  4. washthe residue was washed with dioxane
  5. concentrationthe combined filtrate was concentrated to dryness
  6. customThe residue obtained
  7. customwas purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-a70306888a8e43aa82bc84400d8b067f
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

Loading…