Water → 2-({[5-(Difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl}sulfanyl)-1,3-oxazole

HRID 1511517Notes

Reaction equation

HRID 1511517 reaction equation
[O:1]1[CH:5]=[CH:4][NH:3][C:2]1=[S:6].N12CCCN=C1CCCCC2.Br[CH2:19][C:20]1[C:21]([C:30]([F:33])([F:32])[F:31])=[N:22][N:23]([CH3:29])[C:24]=1[O:25][CH:26]([F:28])[F:27].O>C(#N)C>[F:28][CH:26]([F:27])[O:25][C:24]1[N:23]([CH3:29])[N:22]=[C:21]([C:30]([F:33])([F:32])[F:31])[C:20]=1[CH2:19][S:6][C:2]1[O:1][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 70592403H-1,3-oxazole-2-thioneHCID 117228384-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole

Product 1

HCID 462224072-({[5-(Difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl}sulfanyl)-1,3-oxazole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
25 °C

Procedure

1,3-Oxazole-2(3H)-thione (2.960 g, 29 mmol; prepared as described in WO 2003/006442 A) is initially charged in 50 ml of acetonitrile. With ice-bath cooling, 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU, 4.81 ml, 32 mmol) is added dropwise. The mixture is stirred at 25° C. for 30 minutes. A solution of 4-(bromomethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole (9.045 g, 29 mmol) dissolved in acetonitrile is added dropwise. The mixture is stirred at 25° C. for a further 4 hours and allowed to stand overnight. For work-up, the reaction mixture is added to water and extracted twice with dichloromethane, and the extracts are then washed with water and finally with saturated NaCl solution. The combined organic phases are dried over magnesium sulfate, filtered off and concentrated. The crude product is purified chromatographically (heptan:ethyl acetate, gradient 10:0 to 7:3). This gives 7.6 g of product (74.9% of theory).

Workup

  1. customprepared
  2. temperatureWith ice-bath cooling
  3. additionis added dropwise
  4. stirringThe mixture is stirred at 25° C. for a further 4 hours
  5. waitto stand overnight
  6. extractionextracted twice with dichloromethane
  7. washthe extracts are then washed with water and finally with saturated NaCl solution
  8. dry with materialThe combined organic phases are dried over magnesium sulfate
  9. filtrationfiltered off
  10. concentrationconcentrated
  11. customThe crude product is purified chromatographically (heptan:ethyl acetate, gradient 10:0 to 7:3)

Sources & evidence

ORD record
ord-4903e8e151044aef94fff6097bddb7d8
Source dataset
uspto-grants-2012_07
Patent number
US08216973B2

Reaction notes

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