Tricyclohexylphosphine → tert-Butyl (4-cyclopropyl-2-methylphenyl)carbamate

HRID 2400275Notes

Reaction equation

HRID 2400275 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([CH3:16])[CH:3]=1.O.[CH:18]1(B(O)O)[CH2:20][CH2:19]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:18]1([C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([CH3:16])[CH:3]=2)[CH2:20][CH2:19]1

Participants

9

Reactant 4

HCID 75806TricyclohexylphosphineHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 23074904N-Boc-4-iodo-2-methylanilineHCID 66762321Cyclopropylboronic acid monohydrate

Product 1

HCID 86665748tert-Butyl (4-cyclopropyl-2-methylphenyl)carbamateYield 86.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl (4-iodo-2-methylphenyl)carbamate (1.04 g), cyclopropylboronic acid monohydrate (422 mg), palladium(II) acetate (35.1 mg), tricyclohexylphosphine (87.5 mg), tripotassium phosphate monohydrate (2.52 g), toluene (8.7 mL), and water (0.87 mL) was stirred at 100° C. for 15 hours. The reaction mixture was left to cool and then diluted with ethyl acetate and filtered through Celite (registered trademark). The filtrate was washed with brine and dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (668 mg). 1H-NMR (CDCl3) δ ppm: 0.55-0.70 (2H, m), 0.80-1.00 (2H, m), 1.51 (9H, s), 1.75-1.90 (1H, m), 2.21 (3H, s), 5.85-6.45 (1H, br), 6.75-7.00 (2H, m), 7.45-7.75 (1H, m).

Workup

  1. waitThe reaction mixture was left
  2. temperatureto cool
  3. filtrationfiltered through Celite (registered trademark)
  4. washThe filtrate was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-1badeb70f9d44589a8fd3ae977055fad
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

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