tert-Butyl acetate → Tert-butyl 3-(6-(1,4-dioxaspiro[4,5]decan-8-yl)pyridin-3-yl)-3-oxopropanoate

HRID 220159Notes

Reaction equation

HRID 220159 reaction equation
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[O:19]1[C:23]2([CH2:28][CH2:27][CH:26]([C:29]3[CH:38]=[CH:37][C:32]([C:33](OC)=[O:34])=[CH:31][N:30]=3)[CH2:25][CH2:24]2)[O:22][CH2:21][CH2:20]1>O1CCCC1>[O:19]1[C:23]2([CH2:24][CH2:25][CH:26]([C:29]3[N:30]=[CH:31][C:32]([C:33](=[O:34])[CH2:2][C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3])=[CH:37][CH:38]=3)[CH2:27][CH2:28]2)[O:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 69060042Methyl 6-(1,4-dioxaspiro[4,5]decan-8-yl)nicotinate

Product 1

HCID 69055727Tert-butyl 3-(6-(1,4-dioxaspiro[4,5]decan-8-yl)pyridin-3-yl)-3-oxopropanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Tert-butyl acetate (2.40 mL, 17.82 mmol) was added to a stirred and cooled (−78° C.) solution of lithium hexamethyldisilazide (17.8 mL, 1 M in tetrahydrofuran) in dry tetrahydrofuran (10 mL). After 30 minutes of stirring at −78° C., a solution of Example 93B (2.47 g, 8.9 mmol) in tetrahydrofuran was added dropwise into the solution. The resulting mixture was stirred for another hour before it was quenched with ammonium chloride and allowed to warm to room temperature. The mixture was partitioned with ether and water and the phases were separated. The organic phase was washed with brine, dried (magnesium sulfate), filtered and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes to provide the title compound as a yellow oil.

Workup

  1. stirringAfter 30 minutes of stirring at −78° C.
  2. stirringThe resulting mixture was stirred for another hour before it
  3. customwas quenched with ammonium chloride
  4. customThe mixture was partitioned with ether and water
  5. customthe phases were separated
  6. washThe organic phase was washed with brine
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-72f60b96c25f4d44b06c61168ce04b4b
Source dataset
uspto-grants-2012_06
Patent number
US08202878B2

Reaction notes

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