Triethylamine → tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}-3,5-difluorophenoxy)-1-methylethyl]carbamate

HRID 1026362Notes

Reaction equation

HRID 1026362 reaction equation
[C:1]([C:3]1[C:20]([F:21])=[CH:19][C:6]([O:7][CH2:8][C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[CH:5][C:4]=1[F:22])#[CH:2].Br[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH:32]2[CH2:34][CH2:33]2)=[CH:26][N:25]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.[Cu](I)I.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:32]1([CH2:31][O:30][C:27]2[CH:28]=[CH:29][C:24]([C:2]#[C:1][C:3]3[C:4]([F:22])=[CH:5][C:6]([O:7][CH2:8][C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:17])[CH3:15])[CH3:10])=[CH:19][C:20]=3[F:21])=[N:25][CH:26]=2)[CH2:33][CH2:34]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 578217962-Bromo-5-(cyclopropylmethoxy)pyridineHCID 86666330tert-butyl [(1S)-2-(4-ethynyl-3,5-difluorophenoxy)-1-methylethyl]carbamate

Product 1

HCID 86666329tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}-3,5-difluorophenoxy)-1-methylethyl]carbamateYield 35.9%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 13169693Triphenylphosphine palladium dichlorideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl [(1S)-2-(4-ethynyl-3,5-difluorophenoxy)-1-methylethyl]carbamate (2.5 g), 2-bromo-5-(cyclopropylmethoxy)pyridine (1.8 g), copper iodide (I) (0.15 g), dichloropalladium-triphenylphosphine (1:2) (0.56 g) and triethylamine (2.2 mL) in toluene (20 mL) was stirred at 100° C. overnight under argon atmosphere. After cooling to room temperature, the mixture was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford the title compound (1.3 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through a pad of Celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3418d85dd2534fa4b0cb79079f66eb44
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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