tert-Butyl 4-formylpiperidine-1-carboxylate → tert-Butyl 4-(1-hydroxyethyl)piperidine-1-carboxylate

HRID 222576Notes

Reaction equation

HRID 222576 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][Mg]Br>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([OH:15])[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 21989903tert-Butyl 4-(1-hydroxyethyl)piperidine-1-carboxylateYield 48.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-tert-butoxycarbonyl-4-piperidinecarboxaldehyde (32.20 g, 151.45 mmol) in tetrahydrofuran at −78° C. is added methyl magnesium bromide (2 M in diethyl ether, 100.96 mL, 302.89 mmol). The reaction is stirred at −78° C. for 4.5 h, and then warmed to −50° C. for 30 min. The reaction is quenched with water at −50° C. and allowed to warm to room temperature for 16 h. The solvents are removed and the material is partitioned between diethyl ether and 0.1 M hydrochloric acid. The mixture is extracted with diethyl ether. The combined organic layers are washed with 0.1 M hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated to dryness. The crude is purified by flash chromatography over silica gel to afford 16.90 g of the title compound as a colourless oil. MS (m/z) 229 (M+1).

Workup

  1. temperaturewarmed to −50° C. for 30 min
  2. customThe reaction is quenched with water at −50° C.
  3. temperatureto warm to room temperature for 16 h
  4. customThe solvents are removed
  5. customthe material is partitioned between diethyl ether and 0.1 M hydrochloric acid
  6. extractionThe mixture is extracted with diethyl ether
  7. washThe combined organic layers are washed with 0.1 M hydrochloric acid, saturated aqueous sodium bicarbonate and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe crude is purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-44d142dab45e4638a87734ee6e9e02ff
Source dataset
uspto-grants-2012_06
Patent number
US08207344B2

Reaction notes

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