Sodium triacetoxyborohydride → 1,1-dimethylethyl ((3R,4S)-3-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)carbamate

HRID 656977Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 656977
CO[CH:3](O)[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:17].CC(N([C@H]1CCNC[C@H]1O)C(=O)[O-])(C)C.[C:34]([O:38][C:39](=[O:48])[NH:40][C@H:41]1[CH2:46][CH2:45][NH:44][CH2:43][C@H:42]1[OH:47])([CH3:37])([CH3:36])[CH3:35].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[OH:47][C@H:42]1[C@@H:41]([NH:40][C:39](=[O:48])[O:38][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:46][CH2:45][N:44]([CH2:3][CH2:4][N:5]2[C:14]3[C:9](=[N:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=3)[CH:8]=[CH:7][C:6]2=[O:17])[CH2:43]1

Komponenten

7

Edukt 4

HCID 5049666Sodium triacetoxyborohydrideHCID 67426921HCID 67426921, VerbindungHCID 866230711,1-dimethylethyl[(3R,4S)-3-hydroxy-4-piperidinyl]carbamateHCID 86635329[7-(methoxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]acetaldehyde methyl hemiacetal

Produkt 1

HCID 585794481,1-dimethylethyl ((3R,4S)-3-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittel

Versuchsvorschrift

[7-(methoxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]acetaldehyde methyl hemiacetal (200 mg, 0.7992 mmol) and 1,1-dimethylethyl[(3R,4S)-3-hydroxy-4-piperidinyl]carbamate (for a synthesis see WO2004058144, Example 5(c), cis-(3-hydroxy-piperidin-4-yl)-carbamic acid tert-butyl ester Enantiomer 1) (173 mg, 1 eq.) were stirred in chloroform (10 ml) plus MeOH (0.5 ml) under argon for 2 h. Sodium triacetoxyborohydride (508 mg, 3 eq.) was added in one portion and the mixture was stirred at rt over the weekend, then quenched by addition of saturated aqueous sodium hydrogen cabonate (20 ml) and extracted with 20% v:v MeOH in DCM (3×200 ml). The organic extractes were combined, dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure to give the crude product, which was purified by column chromatography on silica, eluted with 0-20% (2M ammonia in MeOH) in DCM. Appropriate fractions were combined and evaporated under reduced pressure to give 1,1-dimethylethyl ((3R,4S)-3-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)carbamate (263 mg) as an off-white foam.

Aufarbeitung

  1. customquenched by addition of saturated aqueous sodium hydrogen cabonate (20 ml)
  2. extractionextracted with 20% v
  3. dry with materialdried over anhydrous magnesium sulphate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto give the crude product, which
  7. customwas purified by column chromatography on silica
  8. washeluted with 0-20% (2M ammonia in MeOH) in DCM
  9. customevaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-0427942d2d8944f1be03d17a2917ec64
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071592B2

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