Ammonia → N-(2-{4-[(tert-Butyldimethylsilanyl)-ethynyl]-phenyl}-1-methyl-ethyl)-acetamide

HRID 76165Notes

Reaction equation

HRID 76165 reaction equation
[C:1]([NH:4][CH:5]([CH3:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](OS(C(F)(F)F)(=O)=O)=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[Si:22]([C:29]#[CH:30])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].C(NC(C)C)(C)C.N>C(#N)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I.ClCCl>[Si:22]([C:29]#[C:30][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][CH:5]([NH:4][C:1](=[O:3])[CH3:2])[CH3:21])=[CH:8][CH:9]=1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

Participants

10

Reactant 4

HCID 222AmmoniaHCID 7912DiisopropylamineHCID 2757281(tert-Butyldimethylsilyl)acetylene2×HCID 86669624Trifluoromethanesulfonic acid 4-(2-acetylamino-propyl)-phenyl ester

Product 1

HCID 68181211N-(2-{4-[(tert-Butyldimethylsilanyl)-ethynyl]-phenyl}-1-methyl-ethyl)-acetamide

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2.40 g (7.38 mmol) trifluoromethanesulfonic acid 4-(2-acetylamino-propyl)-phenyl ester (I53.1), 1.52 mL (8.12 mmol) (tert-butyldimethylsilyl)acetylene and 2.56 mL (18.4 mmol) diisopropylamine in 25 mL ACN are added 72.3 mg (0.089 mmol) [1,1′bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane and 17.2 mg (0.09 mmol) CuI, and the mixture is stirred at r.t. for 24 h. Again 0.69 mL (3.69 mmol) (tert-butyldimethyl-silyl)acetylene are added and stirring is continued for additional 24 h. The mixture is poured onto aq. ammonia solution (5%), diluted with EtOAc and the organic layer is separated. The organic layer is washed with diluted aq. ammonia solution (1×) and water (1×), dried with MgSO4 and the solvent is removed in vacuo. The residue is purified by column chromatography (silica gel; PE/EtOAc 2/8).

Workup

  1. stirringstirring
  2. waitis continued for additional 24 h
  3. customthe organic layer is separated
  4. washThe organic layer is washed with diluted aq. ammonia solution (1×) and water (1×)
  5. dry with materialdried with MgSO4
  6. customthe solvent is removed in vacuo
  7. customThe residue is purified by column chromatography (silica gel; PE/EtOAc 2/8)

Sources & evidence

ORD record
ord-09510df3e7fb4d3789ecb37e5c37b49d
Source dataset
uspto-grants-2014_09
Patent number
US08835472B2

Reaction notes

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