Ethyl bromodifluoroacetate → (S)-Ethyl 2,2-difluoro-2-(2'-oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetate

HRID 588730Notes

Reaction equation

HRID 588730 reaction equation
I[C:2]1[CH2:7][NH:6][C:5]2[CH2:8][C@@:9]3([CH2:27][C:4]=2[CH:3]=1)[C:17]1[C:12](=[N:13][CH:14]=[CH:15][CH:16]=1)[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:10]3=[O:26].Br[C:29]([F:36])([F:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31]>CS(C)=O.[Cu]>[F:35][C:29]([F:36])([C:2]1[CH:3]=[C:4]2[CH2:27][C@@:9]3([C:17]4[C:12](=[N:13][CH:14]=[CH:15][CH:16]=4)[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:23])[CH3:24])[C:10]3=[O:26])[CH2:8][C:5]2=[N:6][CH:7]=1)[C:30]([O:32][CH2:33][CH3:34])=[O:31]

Participants

5

Reactant 2

HCID 69585Ethyl bromodifluoroacetateHCID 131734438(S)-3-iodo-1'-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1H)-one2×

Product 1

HCID 131734437(S)-Ethyl 2,2-difluoro-2-(2'-oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetate

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

Copper bronze (0.522 g, 8.22 mmol) was added to a solution of (S)-3-iodo-1′-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1H)-one (described in Intermediate 7) (0.811 g, 1.644 mmol) and ethyl bromodifluoroacetate (1.056 mL, 8.22 mmol) in DMSO (10 mL) at ambient temperature. The resulting mixture was heated to 100° C. and stirred for 4 h. The reaction was cooled, partitioned between water (40 mL) and EtOAc (200 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (30 mL). The combined organic extracts were washed with brine, then 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 hexanes:EtOAc—85:15 to 0:100, to give the title compound. MS: m/z=489.1 (M+1).

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between water (40 mL) and EtOAc (200 mL)
  3. customThe organic layer was removed
  4. extractionthe aqueous phase was extracted further with EtOAc (30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with a gradient of hexanes

Sources & evidence

ORD record
ord-d0fe9510b33d45e0bdff3d6782dc0fc9
Source dataset
uspto-grants-2016_01
Patent number
US09227972B2

Reaction notes

Loading…