Nitrogen → 5-(4-Amino-2-nitro-phenyl)-2-methyl-furan-3-carboxylic acid methyl ester

HRID 2075926Notes

Reaction equation

HRID 2075926 reaction equation
N#N.[CH3:3][O:4][C:5]([C:7]1[CH:11]=[C:10](Br)[O:9][C:8]=1[CH3:13])=[O:6].[N+:14]([C:17]1[CH:18]=[C:19]([NH2:32])[CH:20]=[CH:21][C:22]=1B1OC(C)(C)C(C)(C)O1)([O-:16])=[O:15].C(=O)(O)[O-].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:3][O:4][C:5]([C:7]1[CH:11]=[C:10]([C:22]2[CH:21]=[CH:20][C:19]([NH2:32])=[CH:18][C:17]=2[N+:14]([O-:16])=[O:15])[O:9][C:8]=1[CH3:13])=[O:6]

Participants

7

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 15534190Methyl 5-bromo-2-methylfuran-3-carboxylateHCID 597857163-Nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 597857135-(4-Amino-2-nitro-phenyl)-2-methyl-furan-3-carboxylic acid methyl esterYield 34.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

(The following reaction is done in a N2 atmosphere.) Dissolve Pd(PPh3)4 (59 mg, 0.05 mmol) and 5-Bromo-2-methyl-furan-3-carboxylic acid methyl ester (23) (447 mg, 2.04 mmol) in DME (3 mL) and stir for 10 min at rt. Add 3-Nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (39) (465 mg, 1.76 mmol) followed by an aqu. 1 M sodium bicarbonate solution (5.10 mL, 5.10 mmol). Degas the reaction mixture carefully, flush with N2 (5 times) and stir for 4.5 h at 90° C. (reflux). Cool reaction mixture to rt, remove organic solvent under reduced pressure and partition the residue between water and EtOAc. Extract the aqu. layer with EtOAc (3 times), wash the combined organic layer with water and brine and dry it with Na2SO4. Purify the obtained crude product by flash chromatography (silica gel, EtOAc/CyH 1+3, later 1+2) to obtain 5-(4-Amino-2-nitro-phenyl)-2-methyl-furan-3-carboxylic acid methyl ester (40) (167 mg, 34%) as a red solid. 1H NMR (400 MHz, CDCl3): 2.57 (s, 3H); 3.81 (s, 3H); 4.05 (br.s, 2H); 6.68 (s, 1H); 6.81 (dd, 1H, J1=8.3 Hz, J2=2.3 Hz); 6.99 (d, 1H, J=2.3 Hz); 7.39 (d, 1H, J=8.3 Hz).

Workup

  1. custom(The following reaction
  2. customDegas the reaction mixture carefully
  3. customflush with N2 (5 times)
  4. stirringstir for 4.5 h at 90° C.
  5. temperature(reflux)
  6. temperatureCool
  7. customreaction mixture to rt
  8. customremove organic solvent under reduced pressure
  9. custompartition the residue between water and EtOAc
  10. extractionExtract the aqu
  11. washlayer with EtOAc (3 times), wash the combined organic layer with water and brine
  12. dry with materialdry it with Na2SO4
  13. customPurify the
  14. customobtained crude product by flash chromatography (silica gel, EtOAc/CyH 1+3, later 1+2)

Sources & evidence

ORD record
ord-1d8510f1b2054c85af056cd96fa062dd
Source dataset
uspto-grants-2011_04
Patent number
US07923473B2

Reaction notes

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