Formaldehyde → 2-[1-(1-Methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenol

HRID 1692341Notes

Reaction equation

HRID 1692341 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]([C:10]3[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=3[OH:20])=[CH:8][CH:7]=[N:6]2)[CH2:2]1.CO.C=O.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH3:25][N:1]1[CH2:2][CH:3]([N:5]2[C:9]([C:10]3[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=3[OH:20])=[CH:8][CH:7]=[N:6]2)[CH2:4]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5049666Sodium triacetoxyborohydrideHCID 1360636202-(1-Azetidin-3-yl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenol

Product 1

HCID 1360636172-[1-(1-Methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenol

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

2-(1-Azetidin-3-yl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenol, (Preparation 856, 190 mg, 0.00067 mol) was stirred in dichloromethane (5 mL), methanol (0.5 mL) and acetic acid (0.1 mL). Aqueous formaldehyde (0.25 mL of 37% wt/vol, 0.00336 mol) was added and the reaction stirred at room temperature for 15 minutes. Sodium triacetoxyborohydride (711 mg, 0.00336 mol) was added and the reaction stirred at room temperature for 4 hours. The solvents were removed in vacuo and the residue dissolved in water. Aqueous ammonium hydroxide (7.5 molar) was added to pH 10 to give a white precipitate. The mixture was extracted with ethyl acetate (1×20 mL). The organic layer was separated and washed with saturated aqueous sodium chloride solution (2×10 mL). The organic layer was separated, dried over anhydrous sodium sulphate, filtered and the solvents removed in vacuo to give the title compound as a foam. (140 mg).

Workup

  1. stirringthe reaction stirred at room temperature for 4 hours
  2. customThe solvents were removed in vacuo
  3. dissolutionthe residue dissolved in water
  4. additionAqueous ammonium hydroxide (7.5 molar) was added to pH 10
  5. customto give a white precipitate
  6. extractionThe mixture was extracted with ethyl acetate (1×20 mL)
  7. customThe organic layer was separated
  8. washwashed with saturated aqueous sodium chloride solution (2×10 mL)
  9. customThe organic layer was separated
  10. dry with materialdried over anhydrous sodium sulphate
  11. filtrationfiltered
  12. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-3d63822083f74986bbdc560bf6a79619
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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