Trifluoroacetic acid → Racemic 4-{[(3S,4R)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

HRID 15359Notes

Reaction equation

HRID 15359 reaction equation
CC([N:5]([C@@H:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[C:20]3=[C:21]([F:29])[CH:22]=[N:23][C:24]4[CH:25]=[CH:26][C:27](=[O:28])[N:18]([C:19]=43)[CH2:17]2)[CH2:11][C@@H:10]1[OH:30])C(=O)[O-])(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:5][C@@H:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[C:20]3=[C:21]([F:29])[CH:22]=[N:23][C:24]4[CH:25]=[CH:26][C:27](=[O:28])[N:18]([C:19]=43)[CH2:17]2)[CH2:11][C@@H:10]1[OH:30]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131728174HCID 131728174, compound

Product 1

HCID 68684481Racemic 4-{[(3S,4R)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of racemic 1,1-dimethylethyl{(3S,4R)-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}carbamate (15.57 g) in dichloromethane (170 ml) was cooled in ice-water, treated with trifluoracetic acid (137 ml), stirred 1 hour at room temperature and evaporated to dryness. After keeping under high vacuum for 1 hour, the crude material was dissolved in methanol and run through a column of Amberlyst A21 basic resin (500 ml) (Sigma-Aldrich Co.), eluting with methanol. The solution containing the product was evaporated and the residue chromatographed on silica gel, eluting with dichloromethane/methanol/0.88 ammonia (9:1:0.1) to give product (8.96 g, 76%).

Workup

  1. customevaporated to dryness
  2. waitAfter keeping under high vacuum for 1 hour
  3. dissolutionthe crude material was dissolved in methanol
  4. washeluting with methanol
  5. additionThe solution containing the product
  6. customwas evaporated
  7. customthe residue chromatographed on silica gel
  8. washeluting with dichloromethane/methanol/0.88 ammonia (9:1:0.1)

Sources & evidence

ORD record
ord-5227c8331d0b4dce93bf2739e19ce181
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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