Acetic Acid → (6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

HRID 1099180Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1099180
[C:1]([BH3-])#[N:2].[Na+].N[C:6]1[CH:7]=[C:8]2[CH2:16][C@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[F:24])[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=1.C=O.[C:28](O)(=O)C>C(#N)C>[F:24][C:18]1[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=1[C@@H:15]1[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=[C:6]([N:2]([CH3:1])[CH3:28])[CH:7]=[C:8]2[CH2:16]1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57911417(6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

Produkt 1

HCID 57911469(6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-olAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

SODIUM CYANOBOROHYDRIDE (242 mg, 3.86 mmol) was added to the Acetonitrile (2 mL) solution of (6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (56 mg, 0.193 mmol) and FORMALDEHYDE (1 mL, 13.43 mmol) at rt. The reaction was stirred at room temperature for 4 hours. ACETIC ACID (0.5 mL, 8.73 mmol) was added to the reaction mixture (Caution: heat generation was observed to cause acetonitrile reflux) and the reaction was stirred overnight. Volatile was removed mostly via vacuum and the crude was added NaOH (1N), extracted with ethyl acetate twice. The ethyl acetate layer was dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 4% gave the desired product (27.6 mg, 45%). MS (ESI)[M+H+]=319.35.

Aufarbeitung

  1. stirringthe reaction was stirred overnight
  2. customVolatile was removed mostly via vacuum
  3. additionthe crude was added NaOH (1N)
  4. extractionextracted with ethyl acetate twice
  5. dry with materialThe ethyl acetate layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-caf00060cac549809a31a5888ca491cb
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143403B2

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