Water → N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-acetamide

HRID 574743Notes

Reaction equation

HRID 574743 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][C:4]=1[C:13]1[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=1.[Br:19]N1C(=O)CCC1=O.O>CN(C)C(=O)C>[Br:19][C:17]1[CH:16]=[N:15][N:14]([CH3:18])[C:13]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10](=[O:12])[CH3:11])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]

Participants

5

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimideHCID 59514683(N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl])acetamide

Product 1

HCID 59514682N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-acetamideYield 96.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl]-acetamide (25.0 kg) in N,N-dimethylacetamide (DMA, 140.5 kg) in a 400 L glass lined jacketed reactor with overhead stirring under nitrogen at 45 to 55° C. internal temperature N-bromosuccinimide (NBS, 19.0 kg) was charged in portions at such a rate as to maintain internal temperature to less than 55° C. The reaction mixture remained a solution at this dilution of DMA and internal temperature of 50.9° C. An “in process check” of the reaction mixture to determine reaction completion after at least 1 hr of stirring at 50° C. showed that the reaction mixture was substantially free of the starting material. Upon cooling of the reaction mixture to an internal temperature of 34° C. water (150 kg) was added in a controlled manner into the reactor to maintain an internal temperature between 40-55° C. A slight exotherm was observed during the reaction quench. The product slurry was then cooled to −5 to 5° C. and filtered through a corrosion resistant filter/dryer. The wetcake was re-slurried, washed with water (2×25 kg), and dried under full house vacuum (˜30 in Hg) with a jacket temperature of 65° C. producing N-[3-(4 bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy phenyl]-acetamide (31.6 kg, 100% purity by HPLC, 96.1% yield).

Workup

  1. additionwas charged in portions at such a rate as
  2. temperatureto maintain internal temperature to less than 55° C
  3. customreaction completion after at least 1 hr
  4. additionwas added in a controlled manner into the reactor
  5. temperatureto maintain an internal temperature between 40-55° C
  6. customquench
  7. temperatureThe product slurry was then cooled to −5 to 5° C.
  8. filtrationfiltered through a corrosion resistant filter/dryer
  9. washwashed with water (2×25 kg)
  10. customdried under full house vacuum (˜30 in Hg) with a jacket temperature of 65° C.

Sources & evidence

ORD record
ord-fff1b127fd7d4e1fafea5ac1f18c1366
Source dataset
uspto-grants-2015_05
Patent number
US09034911B2

Reaction notes

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