Aluminium lithium hydride → tert-Butyl 3-(hydroxymethyl)piperidine-1-carboxylate

HRID 2353149Notes

Reaction equation

HRID 2353149 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([CH:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)=O>C1COCC1>[C:20]([O:19][C:17]([N:13]1[CH2:14][CH2:15][CH2:16][CH:11]([CH2:9][OH:8])[CH2:12]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 235906521-tert-Butyl 3-methyl piperidine-1,3-dicarboxylate

Product 1

HCID 2763851tert-Butyl 3-(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of lithium aluminium hydride (1.41 g) in THF (15 mL) at 0° C. was added piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester as a solution in THF (10 mL) and the mixture stirred at room temperature for 3 h. The reaction was cooled to 0° C. and quenched by addition of aqueous ammonium chloride and the mixture filtered through celite. The filtrate was diluted with ethyl acetate, washed with water, separated and dried (MgSO4). The solvent was evaporated to give 3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (1.25 g). To a solution of this alcohol (422 mg) in THF (8 mL) was added sodium hydride (94 mg; 60% dispersion in mineral oil). After 15 min iodomethane (0.49 mL) was added and the reaction stirred for 18 h. The mixture was then diluted with ethyl acetate and washed sequentially with water, brine, separated and dried (MgSO4). The solvent was evaporated and the residue purified by flash chromatography to give 3-methoxymethyl-piperidine-1-carboxylic acid tert-butyl ester (414 mg). To a solution of 3-methoxymethyl-piperidine-1-carboxylic acid tert-butyl ester (204 mg) in DCM (3 mL) was added 2M hydrogen chloride in diethyl ether and the mixture stirred for 18 h. The solvent was evaporated to give the desired amine (168 mg).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched by addition of aqueous ammonium chloride
  3. filtrationthe mixture filtered through celite
  4. additionThe filtrate was diluted with ethyl acetate
  5. washwashed with water
  6. customseparated
  7. dry with materialdried (MgSO4)
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-99443a7bbf844b92b22756678d2bf192
Source dataset
uspto-grants-2010_07
Patent number
US07750002B2

Reaction notes

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