Triethylamine → 5-(4-Fluoro-3-hydroxy-benzylcarbamoyl)-3-methyl-thiophene-2-carboxylic acid methyl ester

HRID 1952643Notes

Reaction equation

HRID 1952643 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]([OH:13])=O)=[CH:8][C:9]=1[CH3:10])=[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.[NH2:55][CH2:56][C:57]1[CH:58]=[CH:59][C:60]([F:64])=[C:61]([OH:63])[CH:62]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11](=[O:13])[NH:55][CH2:56][C:57]2[CH:58]=[CH:59][C:60]([F:64])=[C:61]([OH:63])[CH:62]=2)=[CH:8][C:9]=1[CH3:10])=[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 207769865-(Aminomethyl)-2-fluorophenolHCID 682266195-(Methoxycarbonyl)-4-methylthiophene-2-carboxylic acid

Product 1

HCID 682268335-(4-Fluoro-3-hydroxy-benzylcarbamoyl)-3-methyl-thiophene-2-carboxylic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-Methyl-thiophene-2,5-dicarboxylic acid 2-methyl ester (220 mg, 1.10 mmol) in anhydrous DMF (10 mL) was added triethylamine (0.46 mL, 3.30 mmol), HBTU (0.63 g, 1.65 mmol), HOBT (178 mg, 1.32 mmol), and 5-Aminomethyl-2-fluoro-phenol (187 mg, 1.32 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 60-80% EtOAc in hexane to afford the desired product (0.3472 g, 98% 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 60-80% EtOAc in hexane

Sources & evidence

ORD record
ord-d2c12040dc27464494d36ca085bc1d53
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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