Water → HCID 67243506, compound

HRID 2422359Notes

Reaction equation

HRID 2422359 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:22]#[N:23])([C:14]2[C:19](F)=[CH:18][C:17]([Cl:21])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[AlH-](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+].[OH-].[Na+].O>C1COCC1.O1CCOCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([C:14]3[C:19](=[CH:18][C:17]([Cl:21])=[CH:16][N:15]=3)[NH:23][CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 16684435Lithium tritertbutoxyaluminohydrideHCID 672412271,1-Dimethylethyl 4-(5-chloro-3-fluoro-2-pyridinyl)-4-cyano-1-piperidinecarboxylate

Product 1

HCID 67243506HCID 67243506, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-chloro-4′-cyano-3-fluoro-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (0.05 g) and lithium tri-tert-butoxyaluminohydride (0.57 ml), 1M solution in THF) in 1-4-dioxane (0.75 ml) was refluxed under nitrogen for 4 hrs. After cooling, 1 N NaOH and H2O and ethyl acetate were added slowly to the mixture at 0° C. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed with saturated sodium bicarbonate, dried (sodium sulfate), filtered and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-triethylamine (75:25:1)] to give 18 mg g (38%) of 6-chloro-4-aza-spiro[indoline-3,4′-piperidine]-1′-carboxylic acid tert-butylester; MS (ES+) 324 (M+H+).

Workup

  1. temperaturewas refluxed under nitrogen for 4 hrs
  2. temperatureAfter cooling
  3. extractionThe aqueous phase was extracted twice with ethyl acetate
  4. washthe combined organic layers were washed with saturated sodium bicarbonate
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by chromatography [SiO2; hexane-ethyl acetate-triethylamine (75:25:1)]

Sources & evidence

ORD record
ord-7b06bbe70ca04627ac2328b39570811c
Source dataset
uspto-grants-2011_06
Patent number
US07960401B2

Reaction notes

Loading…