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 588999Notes

Reaction equation

HRID 588999 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:EtOAc 100:0 to 50:50

Sources & evidence

ORD record
ord-ddc52a8eb55040bfad78c4942c86114f
Source dataset
uspto-grants-2016_01
Patent number
US09227973B2

Reaction notes

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