Methyl iodide → 4-bromo-3-(4-chlorophenyl)-1-methyl-1H-pyrazole

HRID 41880Notes

Reaction equation

HRID 41880 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[CH3:7]I.[Br:9][C:10]1[CH:11]=[N:12][N:13](C)[C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1>CN(C=O)C>[Br:9][C:10]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[N:13][N:12]([CH3:7])[CH:11]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 67972000HCID 67972000, compound

Product 1

HCID 679719184-bromo-3-(4-chlorophenyl)-1-methyl-1H-pyrazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cs2CO3 (38.0 g, 116.0 mmol) was added to a solution of Ex 3-Step 1 product (15.0 g, 58.0 mmol) in DMF (63 mL). Methyl iodide (3.74 mL, 58.2 mmol) was added and the resulting pink colored solution was stirred at rt for 2 hr. The mixture was concentrated and the residue was partitioned between EtOAc and water. The organic phase was separated and washed with brine, dried (MgSO4) and concentrated. Silica gel chromatography using 40% heptane/CH2Cl2 yielded 10.1 g (64%) of Ex 3-Step 2 product as a white solid. 1H NMR (CDCl3) showed ˜5% of the corresponding regioisomer (4-bromo-5-(4-chlorophenyl)-1-methyl-1H-pyrazole). The identities of the two regiosomers were established via NMR NOE (Nuclear Overhauser Effect) experiments. This material was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.80-7.82 (m, 2H), 7.43 (s, 1H), 7.35-7.38 (m, 2H), 3.90 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between EtOAc and water
  3. customThe organic phase was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customyielded 10.1 g (64%) of Ex 3-Step 2 product as a white solid
  8. customThis material was used without further purification

Sources & evidence

ORD record
ord-78d4d9682339425d91366e2afdb11db9
Source dataset
uspto-grants-2013_09
Patent number
US08536164B2

Reaction notes

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