Benzyl chloroformate → Benzyl 4-(hydroxymethyl)piperidine-1-carboxylate

HRID 2303625Notes

Reaction equation

HRID 2303625 reaction equation
CCN(C(C)C)C(C)C.[OH:10][CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.Cl[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>C(Cl)Cl.C(OCC)(=O)C>[CH2:22]([O:21][C:19]([N:15]1[CH2:16][CH2:17][CH:12]([CH2:11][OH:10])[CH2:13][CH2:14]1)=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 4207714-Piperidinemethanol

Product 1

HCID 736490Benzyl 4-(hydroxymethyl)piperidine-1-carboxylateYield 95.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (4.6 mL, 3.4 g, 26 mmol) was added to a solution of 4-(hydroxymethyl)piperidine (2.00 g, 17.4 mmol) dissolved in methylene chloride (20 mL). The solution was cooled in an ice bath and benzyl chloroformate (2.5 mL, 3.0 g, 18 mmol) was added dropwise over 10 min. After warming to rt and stirring for 96 h, the mixture was diluted with ethyl acetate (50 mL) and washed in succession with 25 mL each of saturated aq. sodium bicarbonate, 2N aq. HCl, saturated aq. sodium bicarbonate, and saturated aq. brine. The organic layer was dried (sodium sulfate), decanted, and evaporated to give 4.14 g of 1-(benzyloxycarbonyl)-4-(hydroxymethyl)piperidine.

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. washwashed in succession with 25 mL each of saturated aq. sodium bicarbonate, 2N aq. HCl, saturated aq. sodium bicarbonate, and saturated aq. brine
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customdecanted
  5. customevaporated

Sources & evidence

ORD record
ord-dedf4130d37443599806db950bd22fe6
Source dataset
uspto-grants-2002_08
Patent number
US06432981B1

Reaction notes

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