N,O-Dimethylhydroxylamine → 4-Phenyl-5-propyl-thiophene-2-carboxylic acid methoxy-methyl-amide

HRID 552295Notes

Reaction equation

HRID 552295 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:12]([OH:14])=O)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li][CH2:16][CH2:17][CH2:18]C.ICCC.CN([C:27]([O:31][N:32]1N=NC2C=CC=C[C:33]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CNOC.CCN(C(C)C)C(C)C>C1COCC1>[CH3:27][O:31][N:32]([CH3:33])[C:12]([C:9]1[S:10][C:11]([CH2:16][CH2:17][CH3:18])=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=1)=[O:14]

Participants

8

Reactant 6

HCID 14232N,O-DimethylhydroxylamineHCID 336431-IodopropaneHCID 81531DiisopropylethylamineHCID 12231844-Phenylthiophene-2-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 178418339Butyllithium

Product 1

HCID 866401764-Phenyl-5-propyl-thiophene-2-carboxylic acid methoxy-methyl-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At −75° C., a solution of 4-phenylthiophene-2-carboxylic acid (1.20 g, 5.88 mmol) in THF (15 mL) is treated with tert.-BuLi (10 mL, 1.6 M in pentane). The mixture is stirred at −70° C. for 1 h before 1-iodopropane (1.5 mL) is added. The reaction mixture is allowed to warm to rt and is stirred overnight. The reaction is quenched with sat. aq. NH4Cl (100 mL) and extracted with DCM (2×200 mL). The solvent of the organic extracts is evaporated and the residue is dissolved in DCM (15 mL). TBTU (2.03 g, 6.33 mmol), N,O-dimethylhydroxylamine (760 mg, 7.80 mmol) and DIPEA (2 mL) is added and the mixture is stirred at rt for 72 h before it is washed with water. The organic layer is separated and evaporated. The residue is purified by CC on silica gel eluting with heptane:EA 5:1 to give 4-phenyl-5-propyl-thiophene-2-carboxylic acid methoxy-methyl-amide (900 mg) as colourless oil; LC-MS: tR=1.05 min, [M+1]+=290.15.

Workup

  1. additionis added
  2. customThe reaction is quenched with sat. aq. NH4Cl (100 mL)
  3. extractionextracted with DCM (2×200 mL)
  4. customThe solvent of the organic extracts is evaporated
  5. dissolutionthe residue is dissolved in DCM (15 mL)
  6. stirringthe mixture is stirred at rt for 72 h before it
  7. washis washed with water
  8. customThe organic layer is separated
  9. customevaporated
  10. customThe residue is purified by CC on silica gel eluting with heptane:EA 5:1

Sources & evidence

ORD record
ord-af76148b6a944ed797ee39936ecee70e
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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