Tetrahydrofuran → HCID 69739267, compound

HRID 985562Notes

Reaction equation

HRID 985562 reaction equation
Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].B(O)O.[C:18]([O-:21])([O-])=O.[Na+].[Na+].[CH2:24]1[CH2:28]O[CH2:26][CH2:25]1>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>[CH3:7][O:6][C:4](=[O:5])[C:3]1[CH:8]=[CH:9][CH:10]=[C:11]([N+:12]([O-:14])=[O:13])[C:2]=1[C:24]1[CH:28]=[CH:11][C:2]2[CH2:3][CH:8]([O:21][CH3:18])[CH2:9][CH2:10][C:26]=2[CH:25]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 10751184Methyl 2-chloro-3-nitrobenzoate

Product 1

HCID 69739267HCID 69739267, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of 5.69 g (26.5 mmol) of methyl 2-chloro-3-nitrobenzoate and 6.00 g (29.1 mmol) of the boronic acid from Part A in 110 mL of THF was treated with 1.68 g of tetrakis(triphenylphosphine)palladium(0) followed by 29.1 mL (58.2 mmol) of 2.0 N Na2CO3. The mixture was flushed with a stream of N2 and heated to mild reflux for 48 hrs. The reaction was allowed to cool and was extracted with EtOAc (5×100 mL). The combined organic layers were washed sequentially with H2O, 1 N aq HCl, saturated aq NaHCO3, and H2O. The organic layers were dried over Na2SO4, filtered and concentrated in vacuo 12.4 g of crude material. The residue was purified by flash chromatography (SiO2; 30% hexanes in toluene to 100% toluene) to afford 3.88 g (43%) of the title compound. 1H NMR (DMSO-d6) δ 8.04 (dd, J=8.1 and 1.1 Hz, 1H), 7.94 (dd, J=7.7 and 1.1 Hz, 1H), 7.68-7.61 (m, 1H), 6.69-6.64 (m, 2H), 3.54 (m, 6H), 2.74-2.67 (m, 2H), 2.61-2.53 (m, 2H), 1.74-1.64 (m, 4H); IR (CHCl3) 2936, 1735, 1535, 1511, 1465, 1298, 1268, 1126 cm−1; FDMS 342 (M+1).

Workup

  1. customThe mixture was flushed with a stream of N2
  2. temperatureheated
  3. temperatureto mild reflux for 48 hrs
  4. temperatureto cool
  5. extractionwas extracted with EtOAc (5×100 mL)
  6. washThe combined organic layers were washed sequentially with H2O, 1 N aq HCl, saturated aq NaHCO3, and H2O
  7. dry with materialThe organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo 12.4 g of crude material
  10. customThe residue was purified by flash chromatography (SiO2; 30% hexanes in toluene to 100% toluene)

Sources & evidence

ORD record
ord-a87abdd753b94bd0be5b4ea62f2f7b9f
Source dataset
uspto-grants-2005_03
Patent number
US06872743B2

Reaction notes

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