Triethylamine → Ethyl 4-(hydroxymethyl)piperidine-1-carboxylate

HRID 704384Notes

Reaction equation

HRID 704384 reaction equation
ClC(OCC)=O.[C:7]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11]1)(O)=[O:8].C(N(CC)CC)C>O1CCCC1>[OH:8][CH2:7][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 66188861-(Ethoxycarbonyl)-4-piperidinecarboxylic Acid

Product 1

HCID 19773576Ethyl 4-(hydroxymethyl)piperidine-1-carboxylateYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.67 g of ethyl chloroformate in 2 ml of tetrahydrofuran was added to a solution of 1.01 g of ethyl 4-carboxypiperidine-1-carboxylate and 0.72 g of triethylamine in 20 ml of tetrahydrofuran at -10° to -5° C., and the mixture was stirred for 30 minutes. The resultant crystalline precipitate was filtered off, the filtrate was added to a solution of 0.57 g of sodium borohydride in 10 ml of water with ice cooling over 30 minutes, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was made acidic with 1N hydrochloric acid with ice cooling and then extracted with ether. The ether layer was washed in sequence with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography. Elution with a hexane-ethyl acetate (1:1 v/v) mixture gave 0.69 g of ethyl 4-hydroxymethylpiperidine-1-carboxylate

Workup

  1. filtrationThe resultant crystalline precipitate was filtered off
  2. additionthe filtrate was added to a solution of 0.57 g of sodium borohydride in 10 ml of water with ice cooling over 30 minutes
  3. stirringthe mixture was stirred at room temperature for 30 minutes
  4. extractionextracted with ether
  5. washThe ether layer was washed in sequence with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washElution with a hexane-ethyl acetate (1:1 v/v) mixture

Sources & evidence

ORD record
ord-c55e03c3715d4187bd2c33d4813e59c9
Source dataset
uspto-grants-1991_01
Patent number
US04987132

Reaction notes

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