(R)-Tert-butyl 2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → tert-butyl (2R)-2-formylpiperidine-1-carboxylate

HRID 529522Notes

Reaction equation

HRID 529522 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].CON(C)[C:10]([C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:11]>CCOCC>[CH:10]([C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:11]

Participants

4

Reactant 2

HCID 10635916(R)-Tert-butyl 2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 10703805tert-butyl (2R)-2-formylpiperidine-1-carboxylateYield 95.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

LiAlH4 (110 mg, 2.89 mmol) was added in portions to a 0° C. solution of (R)-tert-butyl 2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (525 mg, 1.93 mmol) in ether (9 mL). The reaction mixture was then stirred at rt for 30 min. The reaction mixture was cooled to 0° C. and carefully quenched by dropwise addition of aqueous 5% KHSO4 (10 mL). The mixture was then extracted with ether (2×15 mL). The organic extracts were combined, washed with 10% aqueous citric acid, 5% aqueous NaHCO3 and saturated aqueous NaCl. The ether was then dried over MgSO4, filtered and concentrated to give (R)-tert-butyl 2-formylpiperidine-1-carboxylate (392 mg, 1.84 mmol, 95% yield) of a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 9.59 (1H, s), 4.71-4.44 (1H, m), 4.12-3.79 (1H, m), 3.05-2.78 (1H, m), 2.17 (1H, d, J=11.5 Hz), 1.73-1.55 (4H, m), 1.46 (9H, s), 1.34-1.18 (1H, m).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customcarefully quenched by dropwise addition of aqueous 5% KHSO4 (10 mL)
  3. extractionThe mixture was then extracted with ether (2×15 mL)
  4. washwashed with 10% aqueous citric acid, 5% aqueous NaHCO3 and saturated aqueous NaCl
  5. dry with materialThe ether was then dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-873b71200dc8454d83427e59be1d99a6
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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