Formaldehyde → Methyl (2s,3s,5s)-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2h)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxylate

HRID 535056Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 535056
[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([C:13]([C@@H:15]3[C@@H:20]([C:21]([O:23][CH3:24])=[O:22])[CH2:19][C@H:18]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=4)[CH2:17][N:16]3[C:32](OC(C)(C)C)=O)=[O:14])[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O.O1CCCC1.C(#N)C.C(N(CC)C(C)C)(C)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[CH3:32][N:16]1[CH2:17][C@@H:18]([O:25][C:26]2[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=2)[CH2:19][C@H:20]([C:21]([O:23][CH3:24])=[O:22])[C@H:15]1[C:13]([N:10]1[CH2:9][CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1)=[O:14]

Komponenten

9

Edukt 7

HCID 712FormaldehydeHCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 1317319271-Tert-butyl 3-methyl (2s,3s,5s)-2-[(4-phenyl-3,6-dihydropyridin-1(2h)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-1,3-dicarboxylate

Produkt 1

HCID 67304754Methyl (2s,3s,5s)-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2h)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

1-tert-butyl 3-methyl (2S,3S,5S)-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-1,3-dicarboxylate (0.09 g, 0.0002 mol) was treated with trifluoroacetic acid (1.0 mL, 0.013 mol) at rt for 1 h. The mixture was then concentrated to dry. The crude secondary amine made above was dissolved in tetrahydrofuran (0.80 mL, 0.0099 mol) and acetonitrile (0.80 mL, 0.015 mol). The mixture was then treated with N,N-diisopropylethylamine (0.061 mL, 0.00035 mol) to adjust the pH to around 7. To the resultant mixture was then added 12.32 M of formaldehyde in water (0.071 mL) followed by sodium triacetoxyborohydride (180 mg, 0.00087 mol). After stirred at rt overnight, the mixture was concentrated to dry in vacuo, diluted with aq. sodium bicarbonate, extracted with EtOAc. The combined organic layers were washed with brine, dried, and evaporated to dry in vacuo. The residue was exposured in high vacuum and then used directly in next step. MS (ESI): (M+H)+=436.1.

Aufarbeitung

  1. concentrationThe mixture was then concentrated
  2. customto dry
  3. concentrationthe mixture was concentrated
  4. customto dry in vacuo
  5. additiondiluted with aq. sodium bicarbonate
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. customdried
  9. customevaporated
  10. customto dry in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-fa1e2c97203b4c3da07aa8bd75253a59
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853243B2

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