2-Methyl-3-butyn-2-ol → 1,1-Dimethylethyl [5-chloro-3-(3-hydroxy-3-methylbut-1-yn-1-yl)-2-methylphenyl]carbamate

HRID 2261985Notes

Reaction equation

HRID 2261985 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](I)[C:5]([CH3:16])=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1.[CH3:18][C:19]([OH:23])([C:21]#[CH:22])[CH3:20]>C(#N)C.[Cu]I.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:22]#[C:21][C:19]([OH:23])([CH3:20])[CH3:18])[C:5]([CH3:16])=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1

Participants

7

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 866175201,1-Dimethylethyl (5-chloro-3-iodo-2-methylphenyl)carbamate

Product 1

HCID 866175211,1-Dimethylethyl [5-chloro-3-(3-hydroxy-3-methylbut-1-yn-1-yl)-2-methylphenyl]carbamateYield 94%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1,1-dimethylethyl (5-chloro-3-iodo-2-methylphenyl)carbamate (610 mg, 1.7 mmol), 2-methyl-3-butyn-2-ol (245 μl, 2.5 mmol), and triphenylphosphine (30 mg, 0.12 mmol) in acetonitrile (2 mL) was deoxygenated for 20 minutes. The solution was cooled to 0° C., followed by the addition of copper(I)iodide (12 mg, 0.07 mmol), and palladium(II)dichloride (13 mg, 0.06 mmol). The mixture was stirred at reflux for 1.5 hours, then cooled to room temperature and concentrated in-vacuo. The resultant residue was partitioned between water and ethyl acetate. The aqueous portion was extracted twice with ethyl acetate. The combined organic portions were washed with brine, dried over sodium sulfate, filtered and concentrated in-vacuo to afford a brown residue which was purified by column chromatography (silica gel, 20% ethyl acetate in hexanes). The product was collected to afford 504 mg, 1.56 mmol (94%) of 1,1-dimethylethyl [5-chloro-3-(3-hydroxy-3-methylbut-1-yn-1-yl)-2-methylphenyl]carbamate as a yellow solid. 1H NMR (400 MHz, CDCl3): 7.36 (d, 1H), 7.06 (d, 1H), 2.26 (s, 3H), 1.63 (s, 6H), 1.41 (s, 9H); MS (EI) for C17H22ClNO3: 324 (MH+).

Workup

  1. temperatureat reflux for 1.5 hours
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in-vacuo
  4. customThe resultant residue was partitioned between water and ethyl acetate
  5. extractionThe aqueous portion was extracted twice with ethyl acetate
  6. washThe combined organic portions were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in-vacuo
  10. customto afford a brown residue which
  11. customwas purified by column chromatography (silica gel, 20% ethyl acetate in hexanes)
  12. customThe product was collected

Sources & evidence

ORD record
ord-6649fe24ba974e0792ef4a3e1e6bc102
Source dataset
uspto-grants-2010_12
Patent number
US07846959B2

Reaction notes

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