Triethylamine → 5-[3-(tert-Butyl-dimethyl-silanyloxy)-benzylcarbamoyl]-3-trifluoromethyl-thiophene-2-carboxylic acid methyl ester

HRID 1952581Notes

Reaction equation

HRID 1952581 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]([OH:16])=O)=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])=[O:4].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[C:58]([Si:62]([CH3:73])([CH3:72])[O:63][C:64]1[CH:65]=[C:66]([CH:69]=[CH:70][CH:71]=1)[CH2:67][NH2:68])([CH3:61])([CH3:60])[CH3:59]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14](=[O:16])[NH:68][CH2:67][C:66]2[CH:69]=[CH:70][CH:71]=[C:64]([O:63][Si:62]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:72])[CH3:73])[CH:65]=2)=[CH:8][C:9]=1[C:10]([F:11])([F:12])[F:13])=[O:4]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222661693-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]benzenemethanamineHCID 682266025-(Methoxycarbonyl)-4-(trifluoromethyl)thiophene-2-carboxylic acid

Product 1

HCID 682271015-[3-(tert-Butyl-dimethyl-silanyloxy)-benzylcarbamoyl]-3-trifluoromethyl-thiophene-2-carboxylic acid methyl esterYield 20.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-Trifluoromethyl-thiophene-2,5-dicarboxylic acid 2-methyl ester (560 mg, 2.20 mmol) in anhydrous DMF (10 mL) was added triethylamine (0.92 mL, 6.6 mmol), HBTU (1.0 g, 2.64 mmol), HOBT (360 mg, 2.64 mmol), and 3-(tert-Butyl-dimethyl-silanyloxy)-benzylamine (630 mg, 2.64 mmol). The mixture was stirred at room temperature 15 h, then quenched by pouring into EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 0-40% EtOAc in hexane to afford the desired product (0.21 g, 20% yield).

Workup

  1. customquenched
  2. additionby pouring into EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography with 0-40% EtOAc in hexane

Sources & evidence

ORD record
ord-ac7fc72a3f7e4ac39497d871d3d6c0b4
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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