Triethylamine → tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamate

HRID 1026316Notes

Reaction equation

HRID 1026316 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]#[CH:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1.I[C:15]1[CH:32]=[CH:31][C:18]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH3:22])=[CH:17][CH:16]=1.C(N(CC)CC)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.CN(C=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]#[C:13][C:15]3[CH:32]=[CH:31][C:18]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH3:22])=[CH:17][CH:16]=3)=[N:10][CH:11]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 580470405-(Cyclopropylmethoxy)-2-ethynylpyridineHCID 86666304tert-butyl [(1S)-2-(4-iodophenoxy)-1-methylethyl]carbamate

Product 1

HCID 86666303tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamateYield 97.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-(cyclopropylmethoxy)-2-ethynylpyridine (591 mg), tert-butyl [(1S)-2-(4-iodophenoxy)-1-methylethyl]carbamate (1.67 g), bis(triphenylphosphine)palladium(II) dichloride (120 mg), copper(I) iodide (32.5 mg), triethylamine (518 mg) and DMF (10 mL) was stirred at 60° C. overnight under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and water, filtered through celite, and the aqueous layer was separated from the organic layer. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a yellow solid (1.40 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate and water
  3. filtrationfiltered through celite
  4. customthe aqueous layer was separated from the organic layer
  5. extractionThe separated aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d64dd34a15b9438b84c5f76deaecb5e4
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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