Tetrahydrofuran → 7-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1026566Notes

Reaction equation

HRID 1026566 reaction equation
O1CCCC1.[Si]([O:23][CH2:24][CH2:25][C@H:26]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1[CH:40]=[CH:39][C:38]([C:41]([N:43]2[CH2:48][CH2:47][CH:46]([N:49]3[C:58]4[C:53](=[N:54][CH:55]=[C:56]([Cl:59])[CH:57]=4)[CH2:52][C:51]([CH3:61])([CH3:60])[C:50]3=[O:62])[CH2:45][CH2:44]2)=[O:42])=[C:37]([F:63])[CH:36]=1)[CH3:27])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[Cl:59][C:56]1[CH:57]=[C:58]2[C:53]([CH2:52][C:51]([CH3:60])([CH3:61])[C:50](=[O:62])[N:49]2[CH:46]2[CH2:45][CH2:44][N:43]([C:41]([C:38]3[CH:39]=[CH:40][C:35]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[O:28][C@H:26]([CH3:27])[CH2:25][CH2:24][OH:23])=[CH:36][C:37]=3[F:63])=[O:42])[CH2:48][CH2:47]2)=[N:54][CH:55]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium FluorideHCID 680062751-{1-[(2'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 683151677-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-oneYield 80.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a tetrahydrofuran solution (11 ml) of 1-{1-[(2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (525 mg) was added at room temperature a tetrahydrofuran solution (1 M, 1.28 ml) of tetrabutylammonium fluoride, followed by stirring for 3 hours. The reaction solution was diluted with ethyl acetate, washed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 7-chloro-1-{1-[(3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (301 mg).

Workup

  1. washwashed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-51f2b013f8044678a597a206eeff365e
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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