Cesium carbonate → 5-(3,3-Dimethyl-but-1-ynyl)-3-[2-(ethoxy-methyl-phosphinoyl)-ethylamino]-thiophene-2-carboxylic acid methyl ester

HRID 1614913Notes

Reaction equation

HRID 1614913 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1I)=[O:4].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:69]([O:71][P:72]([CH2:75][CH2:76][NH2:77])([CH3:74])=[O:73])[CH3:70]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH:77][CH2:76][CH2:75][P:72]([O:71][CH2:69][CH3:70])([CH3:74])=[O:73])=[O:4]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 581139365-(3,3-Dimethyl-but-1-ynyl)-3-iodo-thiophene-2-carboxylic acid methyl esterHCID 85676205Ethyl (2-aminoethyl)(methyl)phosphinate

Product 1

HCID 670343375-(3,3-Dimethyl-but-1-ynyl)-3-[2-(ethoxy-methyl-phosphinoyl)-ethylamino]-thiophene-2-carboxylic acid methyl esterYield 66%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-iodo-thiophene-2-carboxylic acid methyl ester (669 mg, 1.92 mmol), Pd(OAc)2 (64 mg, 0.288 mmol), BINAP (179 mg, 0.288 mmol), and Cs2CO3 (1.56 g, 4.8 mmol) were combined in a sealed tube. A solution of (2-amino-ethyl)-methyl-phosphinic acid ethyl ester (578 mg, 3.85 mmol) in toluene (14 mL), which had been degassed by bubbling argon through it for 30 minutes, was added. The sealed tube was purged with argon and then sealed. The tube was placed in a 120° C. oil bath. The reaction was stirred overnight, then cooled to room temperature and filtered through filter paper. The residue was stirred vigorously with EtOAc and then the EtOAc was passed through filter paper. The combined filtrates were concentrated and 5-(3,3-Dimethyl-but-1-ynyl)-3-[2-(ethoxy-methyl-phosphinoyl)-ethylamino]-thiophene-2-carboxylic acid methyl ester (466 mg, 66%) was isolated by silica gel column chromatography (MeOH/EtOAc) as a green crystalline solid.

Workup

  1. customby bubbling argon through it for 30 minutes
  2. additionwas added
  3. customThe sealed tube was purged with argon
  4. customsealed
  5. customwas placed in a 120° C.
  6. filtrationfiltered
  7. filtrationthrough filter paper
  8. stirringThe residue was stirred vigorously with EtOAc
  9. filtrationthrough filter paper
  10. concentrationThe combined filtrates were concentrated

Sources & evidence

ORD record
ord-f9d663a4321a4f2893796f8e2916c058
Source dataset
uspto-grants-2014_07
Patent number
US08765722B2

Reaction notes

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