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

HRID 1386764Notes

Reaction equation

HRID 1386764 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.CCOC(C)=O>[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

DIEA (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 CH2Cl2 (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 EtOAc (50 mL) and washed in succession with 25 mL each of saturated aq. NaHCO3, 2 N HCl, saturated aq. NaHCO3, and saturated aq. NaCl. The organic layer was dried (Na2SO4), 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. NaHCO3, 2 N HCl, saturated aq. NaHCO3, and saturated aq. NaCl
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customdecanted
  5. customevaporated

Sources & evidence

ORD record
ord-e42002d2e6ff4fa2b8a1f04315253867
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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