Water → Tert-butyl 4-{[(tert-butoxy)carbonyl]amino}-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 2406005Notes

Reaction equation

HRID 2406005 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([C:20](O)=[O:21])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].O.[OH-].[Na+]>O1CCCC1>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([CH2:20][OH:21])[CH2:16][CH2:15]1)=[O:13])([CH3:9])([CH3:10])[CH3:8]

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 45139438Tert-butyl 4-{[(tert-butoxy)carbonyl]amino}-4-(hydroxymethyl)piperidine-1-carboxylateYield 49.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1M solution of lithium aluminium hydride in tetrahydrofuran (1.66 mL, 1.66 mmol) was added dropwise to a cooled (0° C.) solution of 4-tert-butoxycarbonylamino-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (400 mg, 1.1 mmol) in dry tetrahydrofuran (5 mL). The solution was stirred for 3 h at rt under nitrogen. Water (172 μL) and 10% sodium hydroxide aq (232 μL) were added and the mixture was stirred for 2 h. Further water (172 □L) was added and the mixture was filtered through a pad of celite and washed with diethyl ether. The crude product was purified by flash column chromatography on silica, eluting with 10% methanol in dichloromethane, to give 4-tert-butoxycarbonylamino-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (178 mg, 0.54 mmol, 49%). LC-MS (LCT2) m/z 353 [M+Na+], Rt 6.67 min.

Workup

  1. stirringthe mixture was stirred for 2 h
  2. filtrationthe mixture was filtered through a pad of celite
  3. washwashed with diethyl ether
  4. customThe crude product was purified by flash column chromatography on silica
  5. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-48f0e40fe3804e18a1bd53e9687a61ee
Source dataset
uspto-grants-2014_08
Patent number
US08809336B2

Reaction notes

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