(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid → (2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(hydroxymethyl)piperidine-1-carboxylate

HRID 876427Notes

Reaction equation

HRID 876427 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:23]([C:34](O)=[O:35])[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12>C1COCC1.CO>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[C@H:23]([CH2:34][OH:35])[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

4

Reactant 1

HCID 67230757(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid

Product 1

HCID 67233955(2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(hydroxymethyl)piperidine-1-carboxylateYield 49%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 53; 0.250 g, 0.511 mmol) was dissolved in THF (5.0 mL) and the mixture was cooled to 0° C. BH3—SMe2 (0.242 mL, 2.55 mmol) was added and the mixture was warmed to ambient temperature and stirred for 27 hours. The reaction was quenched with MeOH (2 mL) and concentrated. The residue was taken up in EtOAc (30 mL), water (5 mL) and a saturated aqueous Na2CO3 solution (5 mL). The layers were mixed and separated and the aqueous phase washed once with CH2Cl2 (10 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. During concentration a precipitate formed which was slurried in MeOH, isolated by filtration and washed with Et2O to give 0.119 g (49%) of the desired product as a pale yellow solid.

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. customThe reaction was quenched with MeOH (2 mL)
  3. concentrationconcentrated
  4. additionThe layers were mixed
  5. customseparated
  6. washthe aqueous phase washed once with CH2Cl2 (10 mL)
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. concentrationDuring concentration a precipitate
  12. customformed which
  13. customisolated by filtration
  14. washwashed with Et2O

Sources & evidence

ORD record
ord-4a96ff5ec2be48d7891da5abb1fdecc8
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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