Hydrochloric Acid → Tert-butyl 4'-oxo-3',4'-dihydrospiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxylate

HRID 1908030Notes

Reaction equation

HRID 1908030 reaction equation
[OH:1][C:2]1[C:3]([C:8](=[O:10])[CH3:9])=[N:4][CH:5]=[CH:6][CH:7]=1.O=[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.N1CCCC1.Cl>CO>[O:10]=[C:8]1[C:3]2=[N:4][CH:5]=[CH:6][CH:7]=[C:2]2[O:1][C:12]2([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[CH2:9]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 140889471-(3-Hydroxypyridin-2-yl)ethan-1-one

Product 1

HCID 58551074Tert-butyl 4'-oxo-3',4'-dihydrospiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-(3-hydroxy-2-pyridyl)ethanone (2.4 g, 18 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (3.5 g, 18 mmol) and pyrrolidine (1.5 mL, 18 mmol) in MeOH (12 mL) was stirred at 80° C. for 2 hours. After cooling to room temperature 1M aqueous HCl was added until pH 4 was reached and the reaction mixture was stirred for further 30 minutes. Methanol was evaporated, the remaining mixture was poured into water, and the pH adjusted to pH 7 with saturated aqueous sodium carbonate. The aqueous phase was extracted with ethyl acetate (3×), washed with brine (3×), dried over sodium sulfate and evaporated to dryness. Purification by silica gel chromatography (50-100% ethyl acetate in hexane) afforded tert-butyl 4′-oxo-3′,4′-dihydrospiro-[piperidine-4,2′-pyrano[3,2-b]pyridine]-1-carboxylate (2.2 g, 40%) as an orange oil that solidified upon standing. ESI-MS m/z calc. 318.2. found 319.3 (M+1)+; Retention time: 1.16 minutes (3 min run).

Workup

  1. additionwas added until pH 4
  2. customMethanol was evaporated
  3. additionthe remaining mixture was poured into water
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  5. washwashed with brine (3×)
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness
  8. customPurification by silica gel chromatography (50-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-bbcdb5000f294be883ae4bfc6a3ac7c8
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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