Acetic Acid → 2-{1-[1-(Diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}-4-fluorophenol

HRID 1402021Notes

Reaction equation

HRID 1402021 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.C(O)(=O)C.CN(C)/[CH:28]=[CH:29]/[C:30]([C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[OH:39])=O>C(O)C>[C:16]1([CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:10]2[CH2:13][CH:12]([N:14]3[C:30]([C:32]4[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=4[OH:39])=[CH:29][CH:28]=[N:15]3)[CH2:11]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5713860(2E)-3-(dimethylamino)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-oneHCID 601459041-Benzhydryl-3-hydrazinylazetidine dihydrochloride

Product 1

HCID 1360636272-{1-[1-(Diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}-4-fluorophenol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

1-(diphenylmethyl)-3-hydrazinoazetidine dihydrochloride (Preparation 690, 1.25 g, 4.30 mmol) was stirred in ethanol (20 ml) and acetic acid (8 ml) for 30 minutes with ice cooling to give a suspension. To this cold suspension was added (2E)-3-(dimethylamino)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-one (Preparation 221, 900 mg, 4.3 mmol), stirred at 0° C. for 1 hour then allowed to warm up to room temperature over 18 hours. The reaction mixture was evaporated and then partitioned between ethyl acetate (100 ml), water (50 ml) and saturated aqueous sodium hydrogencarbonate solution (30 ml). The organic layer was separated and back-washed with saturated aqueous sodium chloride solution (2×20 ml), dried over sodium sulphate, filtered and evaporated. The solid was triturated with diethyl ether and the off-white solid filtered. The solid was crystallized from ethyl acetate:hexane (1:4) to give the title compound as colourless crystals were. Yield 490 mg 29%.

Workup

  1. temperatureto warm up to room temperature over 18 hours
  2. customThe reaction mixture was evaporated
  3. custompartitioned between ethyl acetate (100 ml), water (50 ml) and saturated aqueous sodium hydrogencarbonate solution (30 ml)
  4. customThe organic layer was separated
  5. washback-washed with saturated aqueous sodium chloride solution (2×20 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe solid was triturated with diethyl ether
  10. filtrationthe off-white solid filtered
  11. customThe solid was crystallized from ethyl acetate:hexane (1:4)

Sources & evidence

ORD record
ord-c7e9c342fb894f218929d05f067c2af1
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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