Ethyl chloroformate → Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate

HRID 1670767Notes

Reaction equation

HRID 1670767 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC)=O.[BH4-].[Na+].[OH-].[Na+]>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:14][OH:15])([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateYield 104.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

1-(tert-Butoxycarbonyl)-4-phenylpiperidine-4-carboxylic acid (Bionet Co., 1.0 g) was dissolved in tetrahydrofuran (10 ml) and triethylamine (0.55 ml), and the mixture was cooled to 0° C. Under ice-cooling, ethyl chloroformate (0.34 ml) was added to the mixture, and the mixture was stirred for 30 min. Sodium borohydride (250 mg) was added and the mixture was stirred for 30 min. The mixture was warmed to room temperature and stirred for 2 hr. After completion of the reaction, 1N sodium hydroxide was added, and the mixture was extracted with ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure to give 4-(hydroxymethyl)-4-phenyl-1-piperidinecarboxylic acid tert-butyl ester (1.0 g, yield 98%).

Workup

  1. temperatureUnder ice-cooling
  2. stirringthe mixture was stirred for 30 min
  3. stirringstirred for 2 hr
  4. additionwas added
  5. extractionthe mixture was extracted with ethyl acetate
  6. customThe organic layer was dried
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-1e17f838c1a948ec95a5eb6ab7f04b48
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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