p-Toluenesulfonic acid monohydrate → N-[2-tert-Butyl-5-(3-oxo-cyclobutyl)-2H-pyrazol-3-yl]-2,2,2-trifluoro-acetamide

HRID 1594404Notes

Reaction equation

HRID 1594404 reaction equation
[C:1]([N:5]1[C:9]([NH:10][C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]([CH:17]2[CH2:20][C:19](OC)([O:21]C)[CH2:18]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O.O.C(Cl)Cl>[C:1]([N:5]1[C:9]([NH:10][C:11](=[O:16])[C:12]([F:14])([F:15])[F:13])=[CH:8][C:7]([CH:17]2[CH2:18][C:19](=[O:21])[CH2:20]2)=[N:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 57525637HCID 57525637, compound

Product 1

HCID 57525638N-[2-tert-Butyl-5-(3-oxo-cyclobutyl)-2H-pyrazol-3-yl]-2,2,2-trifluoro-acetamideYield 76%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a stirring solution of N-[2-tert-butyl-5-(3,3-dimethoxy-cyclobutyl)-2H-pyrazol-3-yl]-2,2,2-trifluoro-acetamide (6.5 g, 18.5 mmol) in acetone (182 mL) and water (61 mL) was added p-toluenesulfonic acid monohydrate (1.8 g, 9.5 mmol) and the reaction mixture was heated to 65° C. After 1.5 hr, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (250 mL), and water (50 mL). The layers were separated and the aqueous layer was back-extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the resulting material was accomplished by trituration with isopropyl ether. The product was collected and dried under reduced pressure to yield the title compound (4.2 g, 76% yield, two crops) as a yellow solid. 400 MHz 1H NMR (CDCl3) d 7.86 (bs, 1H), 6.33 (s, 1H), 3.62 (dddd, J=7.6, 7.6, 7.6, 7.6 Hz, 1H), 3.46-3.30 (m, 4H), 1.62 (s, 9H). LRMS m/z (APCI+) 304 (M+1).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was back-extracted with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the resulting material
  8. customThe product was collected
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-f3a214b0c9114fdaad65ac78d00e7eab
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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