2,2-Dimethyl-1,3-dioxane-4,6-dione → 2-Hydroxy-4-(2-oxo-6-phenyl-5-(thiophen-3-yl)-1,2,3,4-tetrahydropyridin-4-yl)benzoic acid

HRID 924645Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 924645
[C:1]1([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:15]([C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[C:19]([OH:27])[CH:18]=1)=O.[CH3:28][C:29]1(C)[O:36]C(=O)CC(=O)O1.C([O-])(C)=O.[NH4+:42]>CC(O)=O>[OH:27][C:19]1[CH:18]=[C:17]([CH:15]2[C:8]([C:9]3[CH:13]=[CH:12][S:11][CH:10]=3)=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[NH:42][C:29](=[O:36])[CH2:28]2)[CH:26]=[CH:25][C:20]=1[C:21]([OH:23])=[O:22]

Komponenten

6

Edukt 4

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 517165Ammonium AcetateHCID 122331131-Phenyl-2-(thiophen-3-yl)ethanone2×HCID 21626741Methyl 4-formyl-2-hydroxybenzoate2×

Produkt 1

HCID 566442892-Hydroxy-4-(2-oxo-6-phenyl-5-(thiophen-3-yl)-1,2,3,4-tetrahydropyridin-4-yl)benzoic acidAusbeute 4,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a mixture of 1-phenyl-2-(thiophen-3-yl)ethanone (Intermediate 6) (300 mg, 1.5 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 5) (325 mg, 1.8 mmol), meldrum's acid (260 mg, 1.8 mmol) and AcONH4 (140 mg, 1.8 mmol) in AcOH (3 mL) was refluxed overnight. The mixture was concentrated in vacuo and the residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 40° C. overnight. The resulting mixture was cooled to room temperature, and then acidified with aq. HCl (2 M, 12 mL) to pH=5. Followed a standard aqueous/EtOAc workup i.e. the mixture was extracted with EtOAc (3 times), washed with brine, then combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound 7 (25 mg, 2-steps yield 4%) as yellow solid. 1H NMR (DMSO-d6 400 MHz): δ 9.60 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.44-7.36 (m, 3H), 7.35-7.26 (m, 3H), 7.22-7.15 (m, 1H), 7.14-6.98 (m, 2H), 6.82-6.74 (m, 1H), 6.25 (d, J=4.8 Hz, 1H), 4.13-4.05 (m, 1H), 3.18 (dd, J=16.2, 8.0 Hz, 1H), 2.46-2.42 (m, 1H). MS (ESI): m/z 391.7 [M+1]+.

Aufarbeitung

  1. temperaturewas refluxed overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. temperatureThe resulting mixture was cooled to room temperature
  4. extractionFollowed a standard aqueous/EtOAc workup i.e. the mixture was extracted with EtOAc (3 times)
  5. washwashed with brine
  6. dry with materialcombined organic layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC (0.1% TFA as additive)

Quellen und Nachweise

ORD-Eintrag
ord-6607242c6f7a4fd09ab62662c6d1ad4f
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09283213B2

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