Ammonia → 2-(1-Azetidin-3-yl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenol

HRID 46377Notes

Reaction equation

HRID 46377 reaction equation
FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:10]=1[C:19]1[N:23]([CH:24]2[CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25]2)[N:22]=[CH:21][CH:20]=1.N.CC1C=CC(COC(NNC(C2C=NC=CN=2)=O)=O)=CC=1>ClCCl.O>[NH:26]1[CH2:25][CH:24]([N:23]2[C:19]([C:10]3[CH:11]=[C:12]([C:15]([F:16])([F:17])[F:18])[CH:13]=[CH:14][C:9]=3[OH:8])=[CH:20][CH:21]=[N:22]2)[CH2:27]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 136063628tert-Butyl 3-[5-(5-trifluoromethyl-2-hydroxyphenyl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

Product 1

HCID 1360636202-(1-Azetidin-3-yl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (4 mL) was added to a stirred solution of tert-butyl 3-{5-[2-hydroxy-5-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}azetidine-1-carboxylate, (Preparation 857, 375 mg, 0.001 mol) in dichloromethane (10 mL) under nitrogen and the solution was stirred for 3 hours. The pink solution was evaporated and the residue dissolved in methanol and then the solvents were removed in vacuo. This was repeated a further two times. The residue was then suspended in diethyl ether and the solvents removed in vacuo to give an off-white foam. The foam was dissolved in water and treated with aqueous ammonia solution (7.5 molar) until pH10 to give a white precipitate. The mixture was extracted with ethyl acetate (6×30 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (2×20 mL), dried over anhydrous sodium sulphate, filtered and the solvents removed in vacuo to give a solid. The solid was triturated with diethyl ether to give the title compound as a white solid (200 mg).

Workup

  1. customThe pink solution was evaporated
  2. dissolutionthe residue dissolved in methanol
  3. customthe solvents were removed in vacuo
  4. customthe solvents removed in vacuo
  5. customto give an off-white foam
  6. customto give a white precipitate
  7. extractionThe mixture was extracted with ethyl acetate (6×30 mL)
  8. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (2×20 mL)
  9. dry with materialdried over anhydrous sodium sulphate
  10. filtrationfiltered
  11. customthe solvents removed in vacuo
  12. customto give a solid
  13. customThe solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-a9ae77906c1249d28ba9cf2b0bc1850d
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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