Potassium Carbonate → tert-Butyl 4-((4-(hydroxymethyl)piperidin-1-yl)methyl)benzoate

HRID 529316Notes

Reaction equation

HRID 529316 reaction equation
Br[CH2:2][C:3]1[CH:15]=[CH:14][C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[CH:5][CH:4]=1.[NH:16]1[CH2:21][CH2:20][CH:19]([CH2:22][OH:23])[CH2:18][CH2:17]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[OH:23][CH2:22][CH:19]1[CH2:20][CH2:21][N:16]([CH2:2][C:3]2[CH:15]=[CH:14][C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[CH:5][CH:4]=2)[CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 4207714-PiperidinemethanolHCID 11414578Tert-butyl 4-(bromomethyl)benzoate

Product 1

HCID 68385465tert-Butyl 4-((4-(hydroxymethyl)piperidin-1-yl)methyl)benzoateYield 95.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 4-(bromomethyl)benzoate (1 g, 3.13 mmol) and piperidin-4-ylmethanol (0.361 g, 3.13 mmol) were dissolved in acetonitrile (25 mL). K2CO3 (1.300 g, 9.40 mmol) was added and the reaction mixture was heated to reflux for 20 min. The reaction mixture was cooled down to room temperature, filtered and evaporated. The resulting solid was partitioned between ethyl acetate (50 mL) and 1 M HCl (50 mL). The layers were separated and the aqueous layer was washed with ethyl acetate and the organic layers were discarded. The aqueous layer was basified with 8 M NaOH to pH˜10 and extracted 2 times with 50 mL of ethyl acetate. The organic layers were combined, washed with brine and dried over MgSO4, filtered and evaporated. tert-Butyl 4-((4-(hydroxymethyl)piperidin-1-yl)methyl)benzoate (0.95 g, 2.99 mmol, 95% yield) was isolated as yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.95 (d, J=8.34 Hz, 2H), 7.39 (d, J=8.08 Hz, 2H), 3.56 (s, 2H), 3.51 (d, J=6.57 Hz, 2H), 2.90 (d, J=11.37 Hz, 2H), 1.94-2.04 (m, 2H), 1.73 (d, J=14.15 Hz, 2H), 1.61 (s, 9H), 1.40-1.56 (m, 2H), 1.30-1.37 (m, 2H); LC-MS Rt=0.67 min; MS (ESI): 306.2 [M+H]+.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 20 min
  3. filtrationfiltered
  4. customevaporated
  5. customThe resulting solid was partitioned between ethyl acetate (50 mL) and 1 M HCl (50 mL)
  6. customThe layers were separated
  7. washthe aqueous layer was washed with ethyl acetate
  8. extractionextracted 2 times with 50 mL of ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-9448028be2d14b5e92805de389b10b93
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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