Hydrochloric Acid → Hydrochloric Acid

HRID 1095760Notes

Reaction equation

HRID 1095760 reaction equation
[F:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:10]=[C:11]([F:33])[CH:12]=[C:13]3[C:18]=2[N:17]=[C:16]([C:19]2[N:23]4[CH:24]=[CH:25][C:26]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[CH:27][C:22]4=[N:21][CH:20]=2)[CH:15]=[CH:14]3)[CH2:6][CH2:5][N:4](C(OCC2C=CC3C(=CC=CC=3)C=2)=O)[CH2:3]1.CCO.CCOC(C)=O.[ClH:57]>O1CCOCC1.[Pd]>[F:33][C:11]1[CH:12]=[C:13]2[C:18](=[C:9]([O:8][C@@H:7]3[CH2:6][CH2:5][NH:4][CH2:3][C@H:2]3[F:1])[CH:10]=1)[N:17]=[C:16]([C:19]1[N:23]3[CH:24]=[CH:25][C:26]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[CH:27][C:22]3=[N:21][CH:20]=1)[CH:15]=[CH:14]2.[ClH:57]

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 21584252Ethanol ethylacetateHCID 66782069(3R,4R)-naphthalen-2-ylmethyl 3-fluoro-4-(6-fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate

Product 2

HCID 313Hydrochloric AcidHCID 452542086-fluoro-8-((3R,4R)-3-fluoropiperidin-4-yloxy)-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinoline

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Pd/C (45 mg, 0.042 mmol) 10% wet was added to a solution of (3R,4R)-naphthalen-2-ylmethyl 3-fluoro-4-(6-fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate (270 mg, 0.42 mmol) in a 1:1 mixture of EtOH/EtOAc (10 mL) and 500 uL of 6 N HCl. The mixture was purged with H2, and then allowed to stir under a balloon of hydrogen for 48 hours. The mixture was filtered through GF paper removing the desired product salt as a precipitate, with the palladium catalyst. The combined solids were washed into a beaker with 30 mL of MeOH and the palladium removed by subsequent filtration through GF filter paper. The organic phase was concentrated in vacuo, followed by flash column chromatography (1-20% MeOH/DCM (4% NH4OH). The resulting product was dissolved in chloroform and subject to four equivalents of 4 M HCl in dioxane. The desired product was then isolated as the bis-HCl salt. MS APCI (+) m/z 455.2 (M+1) detected.

Workup

  1. customThe mixture was purged with H2
  2. filtrationThe mixture was filtered through GF paper
  3. customremoving the desired product salt as a precipitate
  4. washThe combined solids were washed into a beaker with 30 mL of MeOH
  5. customthe palladium removed by subsequent filtration through GF
  6. filtrationfilter paper
  7. concentrationThe organic phase was concentrated in vacuo
  8. dissolutionThe resulting product was dissolved in chloroform

Sources & evidence

ORD record
ord-49b33ae92afe4674a312860708b6ea53
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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