Methyl 4-aminobenzoate → Methyl 4-{[(5-chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methyl]amino}benzoate

HRID 2091262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2091262
[Cl:1][C:2]1[N:7]=[C:6]2[C:8]([CH3:19])=[C:9]([C:11]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)=O)[O:10][C:5]2=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[N:7]=[C:6]2[C:8]([CH3:19])=[C:9]([CH:11]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=3)[CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[O:10][C:5]2=[CH:4][CH:3]=1

Komponenten

10

Edukt 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 86662745(5-Chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methanone

Produkt 1

HCID 86662746Methyl 4-{[(5-chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methyl]amino}benzoateAusbeute 88,1 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24193Titanium TetrachlorideKatalysatorHCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a mixture of (5-chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methanone (1.00 g) synthesized above, methyl 4-aminobenzoate (599 mg), triethylamine (4.01 mL) and methylene chloride (10 mL) was added a 1.0M solution (4.32 mL) of titanium (IV) chloride in methylene chloride at 0° C., and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown oil. To a solution (15 mL) of the obtained oil in tetrahydrofuran were added acetic acid (1.03 mL) and sodium cyanoborohydride (452 mg), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-40% ethyl acetate/hexane) to give the title object compound (1.31 g, 81%) as an orange solid.

Aufarbeitung

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark brown oil
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. customto quench
  10. customthe reaction
  11. extractionthe reaction mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (0-40% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-d09eab8a0f5e4825b07876645912a048
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436043B2

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