Carbon tetrabromide → tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate

HRID 1978330Notes

Reaction equation

HRID 1978330 reaction equation
N1CCC(CO)CC1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.O[CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1.C(Br)(Br)(Br)[Br:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.C(#N)C>[Br:40][CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1

Participants

8

Reactant 5

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 90495Di-tert-butyl dicarbonateHCID 4207714-PiperidinemethanolHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5.792 g (50.287 mM) of 4-piperidylmethanol in 150 ml of dichloromethane was added 12.1 g (55.3 mM) of di-tert-butyl dicarbonate dropwise at room temperature and the mixture was stirred at the prevailing temperature overnight. The solvent was then distilled off under reduced pressure to recover crude tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate. This crude product was not purified but used as it was in the next reaction. To a solution of the above crude tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate and 18.3 g (55.3 mM) of carbon tetrabromide in 100 ml of acetonitrile was added 14.5 g (55.3 mM) of triphenylphosphine at room temperature and the mixture was stirred at the prevailing temperature for 3 hours. The solvent was then distilled off under reduced pressure. To the residue was added diethyl ether, and after stirring, the resulting precipitate (triphenylphosphine oxide) was filtered off and washed with diethyl ether. The filtrate and washes were combined and concentrated and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=30/1 to 15/1 to 9/1) to provide the title compound.

Workup

  1. distillationThe solvent was then distilled off under reduced pressure
  2. customto recover crude tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate
  3. customThis crude product was not purified
  4. customwas in the next reaction
  5. stirringthe mixture was stirred at the prevailing temperature for 3 hours
  6. distillationThe solvent was then distilled off under reduced pressure
  7. additionTo the residue was added diethyl ether
  8. stirringafter stirring
  9. filtrationthe resulting precipitate (triphenylphosphine oxide) was filtered off
  10. washwashed with diethyl ether
  11. concentrationconcentrated
  12. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=30/1 to 15/1 to 9/1)

Sources & evidence

ORD record
ord-b9e95c85873a4b6898a76327df58613a
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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