Dimethylformamide → (3-Chloro-2-nitrophenyl)(m-tolyl)methanone

HRID 921260Notes

Reaction equation

HRID 921260 reaction equation
[Cl:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[C:25]1([CH3:33])[CH:30]=[CH:29][CH:28]=[C:27]([Mg]Br)[CH:26]=1>O1CCCC1>[Cl:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([C:5]([C:27]2[CH:26]=[C:25]([CH3:33])[CH:30]=[CH:29][CH:28]=2)=[O:7])[CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 209023-Chloro-2-nitrobenzoic acidHCID 65578Oxalyl chlorideHCID 178425413HCID 178425413, compound2×

Product 1

HCID 86713380(3-Chloro-2-nitrophenyl)(m-tolyl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-chloro-2-nitrobenzoic acid (2.5 g, 12.40 mmol) in tetrahydrofuran (50 mL) was treated with oxalyl chloride (1.194 mL, 13.64 mmol) followed by DMF (0.096 mL, 1.240 mmol). The reaction mixture was stirred at room temperature for 2 hrs. After cooling to 0° C., a 1M solution of m-tolylmagnesium bromide (24.81 mL, 24.81 mmol) was added. After 1 hr another portion of m-tolylmagnesium bromide (24.81 mL, 24.81 mmol) was added. After 1 hour, the reaction mixture was partitioned between ethyl acetate (200 mL) and 1N HCl (150 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 120 g) to provided Intermediate A-18A (0.700 g, 21%). 1H NMR (400 MHz, DMSO-d6) δ 8.04 (dd, J=8.1, 1.1 Hz, 1H), 7.82 (t, J=7.9 Hz, 1H), 7.71 (dd, J=7.7, 1.1 Hz, 1H), 7.66-7.54 (m, 3H), 7.52-7.46 (m, 1H), 2.40 (s, 3H).

Workup

  1. temperatureAfter cooling to 0° C.
  2. waitAfter 1 hour
  3. customthe reaction mixture was partitioned between ethyl acetate (200 mL) and 1N HCl (150 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 120 g)
  9. customto provided Intermediate A-18A (0.700 g, 21%)

Sources & evidence

ORD record
ord-02affd7d6610405f80acbe71a98d3515
Source dataset
uspto-grants-2016_03
Patent number
US09273014B2

Reaction notes

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