Tri-o-tolylphosphine → Tert-butyl 3-(3-(cyclopropylethynyl)phenyl)propylcarbamate

HRID 658844Notes

Reaction equation

HRID 658844 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[CH:6][CH:7]=1.[CH:19]1([C:22]#[CH:23])[CH2:21][CH2:20]1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C1(C)C=CC=CC=1.C(NC(C)C)(C)C.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.[Cu]I>[CH:19]1([C:22]#[C:23][C:2]2[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[CH:6][CH:7]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 138823CyclopropylacetyleneHCID 57219374Tert-butyl 3-(3-bromophenyl)propylcarbamate

Product 1

HCID 58035687Tert-butyl 3-(3-(cyclopropylethynyl)phenyl)propylcarbamate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolventHCID 7912DiisopropylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of tert-butyl 3-(3-bromophenyl)propylcarbamate (57) (1.0 g, 3.1 mmol) and cyclopropyl acetylene (2.9 mL, 3.4 mmol, 70% soln in toluene) in diisopropylamine (4 mL) was added PdCl2(PPh3)2 (0.120 g, 0.17 mmol), tri-o-tolylphosphine (0.048 g, 0.16 mmol) and CuI (0.026 g, 0.16 mmol). The resulting mixture was degassed and stirred under nitrogen at 90° C. for overnight. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by flash chromatography (10-40% ethyl acetate-hexane gradient) gave tert-butyl 3-(3-(cyclopropylethynyl)phenyl)propylcarbamate. Yield (0.756 g, 79%). This alkyne was used for deprotection without futher purification.

Workup

  1. customThe resulting mixture was degassed
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between water and ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (10-40% ethyl acetate-hexane gradient)

Sources & evidence

ORD record
ord-748b5e92a8b247ab965c608f12f6c5ae
Source dataset
uspto-grants-2011_12
Patent number
US08076516B2

Reaction notes

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