Nitrogen → [5-(3-Nitro-phenyl)-thiophen-2-yl]acetic acid methyl ester

HRID 1256689

Reaction equation

HRID 1256689 reaction equation
N#N.[CH3:3][O:4][C:5](=[O:13])[CH2:6][C:7]1[S:8][C:9](Br)=[CH:10][CH:11]=1.[N+:14]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1)([O-:16])=[O:15].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:3][O:4][C:5](=[O:13])[CH2:6][C:7]1[S:8][C:9]([C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:14]([O-:16])=[O:15])[CH:22]=2)=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 16773-Nitrophenylboronic AcidHCID 10340Sodium CarbonateHCID 12403315Methyl 2-(5-bromothiophen-2-yl)acetate

Product 1

HCID 59786790[5-(3-Nitro-phenyl)-thiophen-2-yl]acetic acid methyl esterYield 58.4%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

FR544 (The following reaction is carried out in an N2 atmosphere.) Dissolve Tetrakis-(triphenylphosphine)-palladium(0) (1.12 g, 0.97 mmol) and ester (43) (4.57 g, 19.44 mmol) in toluene (200 mL) and EtOH (20.0 mL), degas the reaction mixture carefully (5 times) and flush with N2. Add 3-nitrophenylboronic acid (3.57 g, 21.38 mmol) and a 3 M aqueous Na2CO3 solution (18.1 mL, 54.3 mmol), degas the reaction mixture again carefully (5 times) and flush with N2. Stir the mixture for 18 h at 100° C. Partition the reaction solution between EtOAc and water and extract the separated aqueous layer with EtOAc (3 times). Wash combined organic layer with brine and dry it with Na2SO4. Purify the obtained crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5) to obtain [5-(3-nitro-phenyl)-thiophen-2-yl]acetic acid methyl ester (56) as a yellow solid (3.15 g, 58%). 1H NMR (400 MHz, CDCl3): 3.75 (s, 3H); 3.85 (s, 2H); 6.94 (br.d, 1H, J=3.8 Hz); 7.27 (d, 1H, J=3.8 Hz); 7.51 (t, 1H, J=8.0 Hz); 7.84 (ddd, 1H, J1=7.8 Hz, J2=1.5 Hz, J3=0.8 Hz); 8.08 (ddd, 1H, J1=8.3 Hz, J2=2.1 Hz, J3=1.0 Hz); 8.39 (t, 1H, J=1.9 Hz).

Workup

  1. customFR544 (The following reaction
  2. customdegas the reaction mixture carefully (5 times)
  3. customflush with N2
  4. customflush with N2
  5. customPartition the reaction solution between EtOAc and water
  6. extractionextract the separated aqueous layer with EtOAc (3 times)
  7. washWash
  8. dry with materialdry it with Na2SO4
  9. customPurify the
  10. customobtained crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5)

Sources & evidence

ORD record
ord-0652c2030faf4ce181f454d758323aba
Source dataset
uspto-grants-2013_06
Patent number
US08461207B2

Linked notes

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