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

HRID 46353Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 46353
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

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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%.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-0050c3ac8bcc40f689df6ccbd8d9a1db
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541588B2

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