Aluminium lithium hydride → 1-Boc-4-(hydroxymethyl)-4-methylpiperidine

HRID 1986177Notes

Reaction equation

HRID 1986177 reaction equation
C[O:2][C:3]([C:5]1([CH3:18])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[C:14]([O:13][C:11]([N:8]1[CH2:9][CH2:10][C:5]([CH2:3][OH:2])([CH3:18])[CH2:6][CH2:7]1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 463183881-tert-Butyl 4-methyl 4-methylpiperidine-1,4-dicarboxylate

Product 1

HCID 232828431-Boc-4-(hydroxymethyl)-4-methylpiperidineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Methylpiperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (1.48 g, 5.73 mmol) is dissolved in THF (15 mL) and cooled to 0° C. 1.0 M lithium aluminum hydride in THF (6.30 mL, 6.30 mmol) is added dropwise. After 1.25 hours the reaction is quenched with MeOH, then stirred with saturated Rochelle's salt until two layers form. The two layers are separated and the aqueous layer is treated with 5 N NaOH and extracted with diethyl ether. The organic layers are combined, concentrated, and chromatographed using silica gel, eluting with EtOAc in hexanes 0-40%, to give the title compound (1.27 g, 97% yield).

Workup

  1. customAfter 1.25 hours the reaction is quenched with MeOH
  2. customThe two layers are separated
  3. additionthe aqueous layer is treated with 5 N NaOH
  4. extractionextracted with diethyl ether
  5. concentrationconcentrated
  6. customchromatographed
  7. washeluting with EtOAc in hexanes 0-40%

Sources & evidence

ORD record
ord-b3b7a539a342463ebf4536bb346429c8
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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