Cyanoacetic acid → 3-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)propanamide

HRID 561847Notes

Reaction equation

HRID 561847 reaction equation
[C:1]([CH2:3][C:4]([N:6]([CH:16]1[CH2:18][CH2:17]1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[Cl:15])=[O:5])#[N:2].CC(O/N=C(/C(NCC=O)=O)\C1N=C(N)SC=1)(C(O)=O)C.C(CC(O)=O)#N.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:56]([Si:60]([O:63][CH2:64][CH2:65][CH2:66][C:67]1[CH:72]=[CH:71][C:70]([CH2:73]I)=[CH:69][CH:68]=1)([CH3:62])[CH3:61])([CH3:59])([CH3:58])[CH3:57]>C1COCC1>[Si:60]([O:63][CH2:64][CH2:65][CH2:66][C:67]1[CH:68]=[CH:69][C:70]([CH2:73][CH:3]([C:1]#[N:2])[C:4]([N:6]([CH:16]2[CH2:17][CH2:18]2)[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=2[Cl:15])=[O:5])=[CH:71][CH:72]=1)([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:62])[CH3:61]

Participants

7

Reactant 5

HCID 9740Cyanoacetic acidHCID 3251421Potassium bis(trimethylsilyl)amideHCID 159566892-[(E)-[1-(2-aminothiazol-4-yl)-2-oxo-2-(2-oxoethylamino)ethylidene]amino]oxy-2-methyl-propanoic acidHCID 66761360tert-Butyl{3-[4-(iodomethyl)phenyl]propoxy}dimethylsilaneHCID 667615892-Cyano-N-cyclopropyl-N-(2,3-dichloro-benzyl)-acetamide

Product 1

HCID 667617693-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)propanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)acetamide (1 eq.), prepared from Amine 2 and cyanoacetic acid as detailed in Step 1 of Example 1, was dissolved in THF (0.1 M). At −78° C., potassium bis(trimethylsilyl)amide (15% w/w toluene solution, 1 eq.) was then added and the resulting yellow suspension was stirred at −78° C. for 15 min and at −40° C. for 15 min. tert-Butyl{3-[4-(iodomethyl)phenyl]propoxy}dimethylsilane from the previous step (1 eq.) was then added, at −78° C., as a 0.33 M THF solution over a period of 10 min. The resulting pale yellow mixture was allowed to warm slowly to RT over 5 h. The reaction was quenched with sat. aq. NH4Cl and extracted with ether. The combined organic extracts were washed with H2O and brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a viscous yellow oil. Purification of the crude product thus obtained by way of column chromatography (SiO2, 10:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a colorless oil.

Workup

  1. customThe reaction was quenched with sat. aq. NH4Cl
  2. extractionextracted with ether
  3. washThe combined organic extracts were washed with H2O and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customConcentration of the filtrate in vacuo afforded a viscous yellow oil
  7. customPurification of the crude product
  8. customthus obtained by way of column chromatography (SiO2, 10:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-1c7ddcf7d0644682b9b562c6f4e3ddeb
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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