Water → Tert-butyl 3'-(hydroxymethylene)-4'-oxo-3',4'-dihydrospiro-[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxylate

HRID 1908031Notes

Reaction equation

HRID 1908031 reaction equation
C[O-].[Na+].[O:4]=[C:5]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[O:8][C:7]2([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:6]1.[CH:27](OCC)=[O:28].O>C1COCC1>[OH:28][CH:27]=[C:6]1[C:7]2([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]2)[O:8][C:9]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[C:5]1=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 8025Ethyl formate2×HCID 10942334Sodium Methoxide2×HCID 58551074Tert-butyl 4'-oxo-3',4'-dihydrospiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxylate

Product 1

HCID 67465078Tert-butyl 3'-(hydroxymethylene)-4'-oxo-3',4'-dihydrospiro-[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxylateYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

To a suspension of sodium methoxide (594 mg, 11.0 mmol) in THF (5 mL) was added a suspension of tert-butyl 4′-oxo-3′,4′-dihydrospiro[piperidine-4,2′-pyrano[3,2-b]pyridine]-1-carboxylate (1.0 g, 3.1 mmol) in THF (10 mL), followed by ethyl formate (2.5 mL, 31 mmol) and the reaction mixture was stirred at 25° C. for 3 hours. Additional sodium methoxide (170 mg, 3.1 mmol) and ethyl formate (0.25 mL, 3.1 mmol) were added and the reaction mixture was stirred at 25° C. for 1 hour. The reaction mixture was poured into water and was extracted with ethyl acetate (4×). The aqueous layer was saturated with solid NaCl and was extracted with ethyl acetate (5×). The organic layers were combined and dried over sodium sulfate. The precipitate formed was filtered and washed with ether (2×). The solid product was dissolved in hot dichloromethane/MeOH (1:1) and filtered, and the filter cake was rinsed with additional hot dichloromethane/MeOH (1:1) (4×) to dissolve all product and remove solid sodium sulfate. The combined filtrates were evaporated to afford tert-butyl 3′-(hydroxymethylene)-4′-oxo-3′,4′-dihydrospiro-[piperidine-4,2′-pyrano[3,2-b]pyridine]-1-carboxylate (560 mg, 52%) as a yellow solid. ESI-MS m/z calc. 346.2. found 347.5 (M+1)+; Retention time: 0.98 minutes (3 min run).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at 25° C. for 1 hour
  3. extractionwas extracted with ethyl acetate (4×)
  4. extractionwas extracted with ethyl acetate (5×)
  5. dry with materialdried over sodium sulfate
  6. customThe precipitate formed
  7. filtrationwas filtered
  8. washwashed with ether (2×)
  9. dissolutionThe solid product was dissolved in hot dichloromethane/MeOH (1:1)
  10. filtrationfiltered
  11. washthe filter cake was rinsed with additional hot dichloromethane/MeOH (1:1) (4×)
  12. dissolutionto dissolve all product
  13. customremove solid sodium sulfate
  14. customThe combined filtrates were evaporated

Sources & evidence

ORD record
ord-fc63880dae29477ba5893708da57a2d5
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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