Methanol → 4-[(Tetrahydro-2H-pyran-4-yl)methoxy]piperidine

HRID 2171621Notes

Reaction equation

HRID 2171621 reaction equation
[Br-].C([N+:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.CO.[BH4-].[Na+]>CC(C)=O>[O:20]1[CH2:19][CH2:18][CH:17]([CH2:16][O:15][CH:12]2[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]2)[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 86686198HCID 86686198, compound

Product 1

HCID 623831894-[(Tetrahydro-2H-pyran-4-yl)methoxy]piperidineYield 97.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

1-Benzyl-4-(tetrahydro-2H-pyran-4-ylmethoxy)pyridinium bromide (1.9 g) was mixed with MeOH (35 ml), and NaBH4 (850 mg) was added thereto, followed by stirring at room temperature for 1 hour. Acetone (6 ml) was added to the reaction mixture, followed by stirring at room temperature for 30 minutes, and then activated carbon (1 g) was added thereto, followed by stirring at room temperature for 30 minutes and filtering using Celite as a filtration adjuvant. The filtrate was concentrated under reduced pressure. EtOAc and a saturated aqueous sodium hydrogen carbonate solution were added to the obtained residue, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was mixed with MeOH (35 ml), and ammonium formate (3 g) and 10% palladium carbon (400 mg) were added thereto, followed by stirring at 50° C. for 4 hours and filtering using Celite, and the filtrate was concentrated under reduced pressure. EtOAc and a saturated aqueous sodium hydrogen carbonate solution were added to the residue, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (CHCl3/MeOH) to obtain 4-(tetrahydro-2H-pyran-4-ylmethoxy)piperidine (1.01 g).

Workup

  1. additionwas added
  2. stirringby stirring at room temperature for 30 minutes
  3. additionactivated carbon (1 g) was added
  4. stirringby stirring at room temperature for 30 minutes
  5. filtrationfiltering
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additionEtOAc and a saturated aqueous sodium hydrogen carbonate solution were added to the obtained residue
  8. dry with materialthe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. additionThe obtained residue was mixed with MeOH (35 ml), and ammonium formate (3 g) and 10% palladium carbon (400 mg)
  11. additionwere added
  12. stirringby stirring at 50° C. for 4 hours
  13. filtrationfiltering
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. additionEtOAc and a saturated aqueous sodium hydrogen carbonate solution were added to the residue
  16. dry with materialthe organic layer was dried over Na2SO4
  17. concentrationconcentrated under reduced pressure
  18. customThe obtained residue was purified by basic silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-a91e0693d0c34da8978b9604628c756b
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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