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

HRID 656974Notes

Reaction equation

HRID 656974 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([C@H]1CCNC[C@H]1O)C(=O)[O-])(C)C.[C:33]([O:37][C:38](=[O:47])[NH:39][C@H:40]1[CH2:45][CH2:44][NH:43][CH2:42][C@H:41]1[OH:46])([CH3:36])([CH3:35])[CH3:34].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:43]2[CH2:44][CH2:45][C@H:40]([NH:39][C:38](=[O:47])[O:37][C:33]([CH3:34])([CH3:35])[CH3:36])[C@H:41]([OH:46])[CH2:42]2)=[N:10][CH:11]=1

Participants

7

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 57815296HCID 57815296, compoundHCID 67426921HCID 67426921, compoundHCID 866230711,1-dimethylethyl[(3R,4S)-3-hydroxy-4-piperidinyl]carbamate

Product 1

HCID 585793371,1-dimethylethyl {(3R,4S)-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[(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) (182 mg, 1 eq.) were stirred in chloroform (10 ml) plus MeOH (0.5 ml) under argon for 2 hours. Sodium triacetoxyborohydride (534 mg, 3 eq.) was added in one portion and the mixture was stirred at rt overnight, 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 title compound (247 mg) as an off-white foam.

Workup

  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

Sources & evidence

ORD record
ord-d986d71f251d42338241d59b5628c95f
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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