Hydrochloric Acid → Tert-butyl 3-(hydroxymethyl)-4-methylpiperidine-1-carboxylate

HRID 1808701Notes

Reaction equation

HRID 1808701 reaction equation
C([O:3][C:4]([CH:6]1[CH:11]([CH3:12])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1.C(OCC)(=O)C>[C:16]([O:15][C:13]([N:8]1[CH2:9][CH2:10][CH:11]([CH3:12])[CH:6]([CH2:4][OH:3])[CH2:7]1)=[O:14])([CH3:18])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 707916011-Tert-butyl 3-ethyl 4-methylpiperidine-1,3-dicarboxylate

Product 1

HCID 58009921Tert-butyl 3-(hydroxymethyl)-4-methylpiperidine-1-carboxylateYield 101%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A flask containing (+/−)-4-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (5.96 g, 21.94 mmol) in dry tetrahydrofuran (40 mL) was cooled to 0° C. (ice bath) under argon atmosphere. A solution of lithium aluminum hydride (19.4 mL, 1M in tetrahydrofuran) was added via slow drop-wise addition. The cooled mixture was stirred for 2 hours. A solution of 1 M hydrochloric acid (23 mL) was added via slow drop-wise addition. After 10 minutes powdered magnesium sulfate was added followed by the addition of ethyl acetate (80 mL). The mixture was filtered through a plug of celite, rinsing well with ethyl acetate. The filtrate was stripped providing 5.08 g of (+/−)-3-hydroxymethyl-4-methyl-piperidine-1-carboxylic acid tert-butyl ester as a clear semi-mobile oil. MS (M+Na)+=252.

Workup

  1. waitAfter 10 minutes powdered
  2. filtrationThe mixture was filtered through a plug of celite
  3. washrinsing well with ethyl acetate

Sources & evidence

ORD record
ord-f0be07b034554cd796d48241f8bd18d6
Source dataset
uspto-grants-2013_01
Patent number
US08361962B2

Reaction notes

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