Triethylamine → 2-(Cyclohexyloxymethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963245Notes

Reaction equation

HRID 1963245 reaction equation
[CH:1]1([O:7][CH2:8][CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[CH:1]1([O:7][CH2:8][CH:9]2[CH2:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 59536557Dimethyl 2-(cyclohexyloxymethyl)piperidine-1,4-dicarboxylate

Product 1

HCID 595365632-(Cyclohexyloxymethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 100.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(cyclohexyloxymethyl)piperidine-1,4-dicarboxylate (2.54 g, 8.1 mmol) was dissolved in acetonitrile (35 mL) and water (0.7 mL), then lithium bromide (5.63 g, 64.80 mmol) was added. Triethylamine (4.49 mL, 32.40 mmol) was added and the resulting suspension was heated under reflux for 4 h. MTBE (100 mL) and water (50 mL) were added, the phases separated and the organic layer was extracted with water. The combined aqueous layers were acidified to pH 1 with 3.8 M HCl and extracted with MTBE. The combined organic layers were dried with Na2SO4 and evaporated. 2-(Cyclohexyloxymethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (2.43 g, quant.) was isolated. MS m/z 300 (M+H)+

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureunder reflux for 4 h
  3. customthe phases separated
  4. extractionthe organic layer was extracted with water
  5. extractionextracted with MTBE
  6. dry with materialThe combined organic layers were dried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-818cedaa229d45f0ac98f636de5b4c76
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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