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

HRID 1486447Notes

Reaction equation

HRID 1486447 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 200 mL round-bottomed flask was charged with 3-chloro-2-nitrobenzoic acid (2.5 g, 12.40 mmol) and tetrahydrofuran (50 mL). Oxalyl chloride (1.194 mL, 13.64 mmol) was added slowly 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 a further hour, the reaction mixture was partitioned between ethyl acetate (200 mL) and 1N HCl (150 mL). The aqueous layer was back extracted with ethyl acetate (2×100 mL). The combined organic phases were dried with 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). Concentration of the appropriate fractions provided Intermediate A-10A (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 hr
  3. waitAfter a further hour
  4. customthe reaction mixture was partitioned between ethyl acetate (200 mL) and 1N HCl (150 mL)
  5. extractionThe aqueous layer was back extracted with ethyl acetate (2×100 mL)
  6. dry with materialThe combined organic phases were dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. 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)
  10. customConcentration of the appropriate fractions provided Intermediate A-10A (0.700 g, 21%)

Sources & evidence

ORD record
ord-c6509c38c45447d6ba4d0d24f1138920
Source dataset
uspto-grants-2016_08
Patent number
US09427442B2

Reaction notes

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