Hydrochloric Acid → 1-((Tert-butoxy)carbonyl)-3-methylpiperidine-3-carboxylic acid

HRID 2409920Notes

Reaction equation

HRID 2409920 reaction equation
[CH3:1][C:2]1([C:15]([O:17]CC)=[O:16])[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[OH-].[Li+].Cl>C1COCC1.CO>[C:11]([O:10][C:8]([N:4]1[CH2:5][CH2:6][CH2:7][C:2]([CH3:1])([C:15]([OH:17])=[O:16])[CH2:3]1)=[O:9])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 205853941-tert-Butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate

Product 1

HCID 186197611-((Tert-butoxy)carbonyl)-3-methylpiperidine-3-carboxylic acidYield 98%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-tert-butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate (15 g, 55.3 mmol) in THF (87 mL) and MeOH (87 mL) was added lithium hydroxide(2M in water) (172 mL, 345 mmol) at RT and stirred at same temperature for 15 h. The reaction mixture was cooled in an ice-bath, and adjusted to pH ˜4 by adding 1N HCl solution. The aqueous layer was extracted with ethylacetate (3×200 mL) and the combined organic extracts was washed with brine (20 mL), dried (Na2SO4), filtered and concentrated to give desired 1-(tert-butoxycarbonyl)-3-methylpiperidine-3-carboxylic acid (13.45 g, 54.2 mmol, 98% yield) as a white solid. This material was directly used for next step with out any further purification. Anal. Calcd. for C12H21NO4 m/z 243.3, found: 242.2 (M−H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 12.31 (s, 1 H) 3.68-3.52 (m, 1 H), 3.32-3.02 (m, 4 H), 1.89-1.82 (m, 1 H), 1.54-1.43 (m, 11 H) 1.06 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was cooled in an ice-bath
  2. extractionThe aqueous layer was extracted with ethylacetate (3×200 mL)
  3. washthe combined organic extracts was washed with brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-770a5e84167947ee8b00f3d2f09a96f8
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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