Hydrochloric Acid → Ethyl (6S)-5'-fluoro-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate

HRID 448251Notes

Reaction equation

HRID 448251 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C@:10]3([CH2:23][C:13]4=[N:14][CH:15]=[C:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:17]=[C:12]4[CH2:11]3)[C:9](=[O:24])[N:8](COCC[Si](C)(C)C)[C:5]2=[N:6][CH:7]=1.Cl.C(N)CN.[OH-].[Na+]>CO.O>[F:1][C:2]1[CH:3]=[C:4]2[C@:10]3([CH2:23][C:13]4=[N:14][CH:15]=[C:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:17]=[C:12]4[CH2:11]3)[C:9](=[O:24])[NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3301EthylenediamineHCID 14798Sodium HydroxideHCID 86665252Ethyl (6S)-5'-fluoro-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate

Product 1

HCID 86665254Ethyl (6S)-5'-fluoro-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of ethyl (6S)-5′-fluoro-2′-oxo-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylate (300 mg, 0.656 mmol) in MeOH (15 mL) was saturated with HCl (g) and aged for 30 min at ambient temperature. The resulting mixture was concentrated to dryness in vacuo. The residue was dissolved in MeOH (10 mL), ethylenediamine (0.044 mL, 0.656 mmol) was added, and the solution was adjusted to pH 10 by addition of 1 N sodium hydroxide. The resulting mixture was stirred at ambient temperature for 30 min, poured into water (20 mL) and extracted with CHCl3 (2×25 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 90:10, to give the title compound, which contained some of the corresponding methyl ester. MS: m/z=328.2 (M+1).

Workup

  1. concentrationThe resulting mixture was concentrated to dryness in vacuo
  2. dissolutionThe residue was dissolved in MeOH (10 mL)
  3. extractionextracted with CHCl3 (2×25 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-f143eeb1b3ee494a815a911593970de8
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Reaction notes

Loading…