Methanol → 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

HRID 448250Notes

Reaction equation

HRID 448250 reaction equation
[O:1]=[C:2]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=[C:8]([Sn](CCCC)(CCCC)CCCC)[CH:9]=[C:4]2[C@@:3]21[CH2:44][C:34]1=[N:35][CH:36]=[C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:38]=[C:33]1[CH2:32]2.C(=O)(O)[O-].[Na+].[B-](F)(F)(F)[F:51].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.FC(F)(F)S([O-])(=O)=O.[Na+].CO>CC(C)=O.[Ag-]=O>[F:51][C:8]1[CH:9]=[C:4]2[C@:3]3([CH2:44][C:34]4=[N:35][CH:36]=[C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:38]=[C:33]4[CH2:32]3)[C:2](=[O:1])[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 516892Sodium Bicarbonate2×HCID 2724933SelectfluorHCID 23676748Sodium trifluoromethanesulfonateHCID 86665253ethyl (6S)-2'-oxo-5'-(tributylstannanyl)-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 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

Reagents, catalysts & solvents 2

HCID 178418778HCID 178418778, compoundCatalystHCID 180AcetoneSolvent

Conditions

Temperature
65 °C

Procedure

A stirred mixture of ethyl (6S)-2′-oxo-5′-(tributylstannanyl)-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylate (1.00 g, 1.37 mmol), sodium bicarbonate (231 mg, 2.74 mmol), silver(I) oxide (32 mg, 0.137 mmol), N-chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate) (972 mg, 2.74 mmol), sodium trifluoromethanesulfonate (236 mg, 1.37 mmol) and methanol (0.278 mL, 6.86 mmol) in acetone (50 mL) in a sealed vessel was heated at 65° C. for 4 h. The resulting mixture was cooled to ambient temperature, poured into saturated aqueous sodium bicarbonate (50 mL) and extracted with EtOAc (2×75 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:EtOAc—100:0 to 50:50, to give the title compound. MS: m/z=458.4 (M+1).

Workup

  1. temperatureThe resulting mixture was cooled to ambient temperature
  2. extractionextracted with EtOAc (2×75 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-44a835d1e65e41329c70d6eee484d0fa
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Reaction notes

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