(E)-1-(5-chloro-2-hydroxyphenyl)-3-(dimethylamino)prop-2-en-1-one → 2-[2-(1-Benzhydryl-azetidin-3-yl)-2H-pyrazol-3-yl]-4-chloro-phenol

HRID 46355Notes

Reaction equation

HRID 46355 reaction equation
Cl.Cl.[C:3]1([CH:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:10]2[CH2:13][CH:12]([NH:14][NH2:15])[CH2:11]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([OH:36])=[C:27]([C:29](=O)/[CH:30]=[CH:31]/N(C)C)[CH:28]=1>C(O)C.C(O)(=O)C.COC(C)(C)C>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([OH:36])=[C:27]([C:29]2[N:14]([CH:12]3[CH2:13][N:10]([CH:9]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:11]3)[N:15]=[CH:31][CH:30]=2)[CH:28]=1

Participants

6

Reactant 2

HCID 33728788(E)-1-(5-chloro-2-hydroxyphenyl)-3-(dimethylamino)prop-2-en-1-oneHCID 601459041-Benzhydryl-3-hydrazinylazetidine dihydrochloride

Product 1

HCID 1360636302-[2-(1-Benzhydryl-azetidin-3-yl)-2H-pyrazol-3-yl]-4-chloro-phenolYield 42%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

1-(diphenylmethyl)-3-hydrazinoazetidine dihydrochloride (Preparation 690, 1.00 g, 3.06 mmol) was added to an ice cold, stirred suspension of (2E)-1-(5-chloro-2-hydroxyphenyl)-3-(dimethylamino)prop-2-en-1-one (Preparation 759, 700 mg, 3.1 mmol) in ethanol (5 ml) and acetic acid (5 ml), stirred at 0° C. for 2 hours then allowed to warm up to room temperature over 2 hours. The solvents were removed in vacuo and the residue partitioned between ethyl acetate (80 ml) and saturated aqueous sodium hydrogencarbonate solution (50 ml). The organic layer was separated and dried over sodium sulphate, filtered and the solvents removed in vacuo to give a yellow gum. This was dissolved in warm methyl-t-butyl ether (20 ml) and allowed to crystallize to give the title compound as a pale yellow powder, 541 mg, yield 42%.

Workup

  1. stirringstirred at 0° C. for 2 hours
  2. customThe solvents were removed in vacuo
  3. customthe residue partitioned between ethyl acetate (80 ml) and saturated aqueous sodium hydrogencarbonate solution (50 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvents removed in vacuo
  8. customto give a yellow gum
  9. customto crystallize

Sources & evidence

ORD record
ord-c6294fca575c4092a2bafe06f394f91c
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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