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

HRID 657009Notes

Reaction equation

HRID 657009 reaction equation
CO[CH:3](O)[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([F:15])[CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:16].CC([N:22]([C@@H:26]1[CH2:31][CH2:30][NH:29][CH2:28][C@@H:27]1[OH:32])[C:23](=[O:25])[O-:24])(C)C.OCC[CH2:36][C:37]1[C:42](=O)N(CC2C=CC(OC)=CC=2)NC(=O)[CH:38]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[F:15][C:12]1[CH:13]=[C:14]2[C:9]([CH:8]=[CH:7][C:6](=[O:16])[N:5]2[CH2:4][CH2:3][N:29]2[CH2:30][CH2:31][C@@H:26]([NH:22][C:23](=[O:25])[O:24][C:37]([CH3:42])([CH3:38])[CH3:36])[C@@H:27]([OH:32])[CH2:28]2)=[N:10][CH:11]=1

Participants

7

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 57815296HCID 57815296, compoundHCID 675265645-(3-Hydroxypropyl)-1-{[4-(methyloxy)phenyl]methyl}-1,2-dihydro-3,6-pyridazinedioneHCID 866353341,1-dimethylethyl[(3S,4R)-3-hydroxy-4-piperidinyl]carbamate

Product 1

HCID 866353331,1-dimethylethyl {(3S,4R)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-3-hydroxy-4-piperidinyl}carbamate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

(7-Fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde methyl hemiacetal (200 mg, 0.8396 mmol) and 1,1-dimethylethyl[(3S,4R)-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 2) (192 mg, 1 eq.) were stirred in chloroform (10 ml) plus MeOH (0.5 ml) under argon for 2 h. Sodium triacetoxyborohydride (534 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 (2 mL). The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×20 ml). The organic extracts 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 {(3S,4R)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-3-hydroxy-4-piperidinyl}carbamate (310 mg) as a tan foam.

Workup

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

Sources & evidence

ORD record
ord-542c1c5ee8c14d1f9017fcdaab79e0d8
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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