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

HRID 1862663Notes

Reaction equation

HRID 1862663 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-c181aeae05124a288e3e5fd2143e81b4
Source dataset
uspto-grants-2003_03
Patent number
US06538002B1

Reaction notes

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