Nitrogen → HCID 59594877, compound

HRID 2075007Notes

Reaction equation

HRID 2075007 reaction equation
COC1C=C2C([C@H]3[C@@](O)(C2)COC2C=C(O)C=CC3=2)=CC=1OC.N#N.[CH3:26][O:27][C:28]([C:30]1[CH:34]=[C:33](Br)[O:32][C:31]=1[CH3:36])=[O:29].CC1(C)C(C)(C)OB([C:45]2[CH:50]=[CH:49][C:48]([NH2:51])=[CH:47][CH:46]=2)O1.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>[CH3:26][O:27][C:28]([C:30]1[CH:34]=[C:33]([C:45]2[CH:50]=[CH:49][C:48]([NH2:51])=[CH:47][CH:46]=2)[O:32][C:31]=1[CH3:36])=[O:29]

Participants

8

Reactant 5

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 11515169HCID 11515169, compoundHCID 15534190Methyl 5-bromo-2-methylfuran-3-carboxylate

Product 1

HCID 59594877HCID 59594877, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

DK002+003 (The following reaction is carried out in a N2 atmosphere.) Dissolve Pd(PPh3)4 (1.26 g, 1.09 mmol) and 5-Bromo-2-methyl-furan-3-carboxylic acid methyl ester (53) (4.77 g, 21.77 mmol) in DME (116 mL) and stir for 15 min at rt. Add 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (5.25 g, 23.96 mmol) followed by an aqu. 1M sodium bicarbonate solution (65.4 mL, 65.3 mmol). Degas the reaction mixture carefully, flush with N2 (5 times) and stir for 4 h at 95° 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+2) to obtain 5-(4-Amino-phenyl)-2-methyl-furan-3-carboxylic acid methyl ester (54) (2.35 g, 46%) as a yellow-brown solid. 1H NMR (400 MHz, CDCl3): 2.60 (s, 3 H); 3.74 (br.s, 2 H); 3.82 (s, 3 H); 6.64 (s, 1 H); 6.67 (dt, 1 H, J1=8.6 Hz, J2=2.3 Hz); 7.42 (dt, 2 H, J1=8.8 Hz, J2=2.3 Hz).

Workup

  1. customDegas the reaction mixture carefully
  2. customflush with N2 (5 times)
  3. stirringstir for 4 h at 95° C.
  4. temperature(reflux)
  5. temperatureCool
  6. customreaction mixture to rt
  7. customremove organic solvent under reduced pressure
  8. custompartition the residue between water and EtOAc
  9. extractionExtract the aqu
  10. washlayer with EtOAc (3 times), wash the combined organic layer with water and brine
  11. dry with materialdry it with Na2SO4
  12. customPurify the
  13. customobtained crude product by flash chromatography (silica gel, EtOAc/CyH 1+2)

Sources & evidence

ORD record
ord-b49e24f4102f4c0289b139f3c8fd9608
Source dataset
uspto-grants-2011_04
Patent number
US07919532B2

Reaction notes

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