Carbon tetrabromide → Benzyl 2-(3-bromopropyl)piperidine-1-carboxylate

HRID 2038163Notes

Reaction equation

HRID 2038163 reaction equation
O[CH2:2][CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].C(Br)(Br)(Br)[Br:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:22][CH2:2][CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58306067Benzyl 2-(3-hydroxypropyl)piperidine-1-carboxylate2×

Product 1

HCID 58306190Benzyl 2-(3-bromopropyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of phenylmethyl 2-(3-hydroxypropyl)-1-piperidinecarboxylate (for example, as prepared for Intermediate 9) (2.14 g, 7.72 mmol) in anhydrous dichloromethane (34 mL) was added carbon tetrabromide (commercially available, for example, from Aldrich) (5.12 g, 15.43 mmol). The resulting solution was cooled in ice/water. A solution of triphenylphosphine (4.05 g, 15.43 mmol) in dry DCM (10 mL) was added dropwise over 30 minutes, producing a deep amber/brown solution. After complete addition, the reaction was allowed to warm slowly to ambient temperature and stirring continued overnight. The reaction mixture was filtered to remove the precipitate, washed with ether and the filtrate evaporated to ˜10 mL. This was then loaded onto a 100 g silica cartridge and purified by chromatography using a gradient of Flashmaster 0-25% ethylacetate in cylcohexane over 40 minutes on a Flashmaster collecting all the eluent. The product peak was identified by TLC and the fractions combined and evaporated in vacuo to give the title compound as a clear oil (2.13 g)

Workup

  1. customproducing a deep amber/brown solution
  2. additionAfter complete addition
  3. filtrationThe reaction mixture was filtered
  4. customto remove the precipitate
  5. washwashed with ether
  6. customthe filtrate evaporated to ˜10 mL
  7. custompurified by chromatography
  8. customover 40 minutes
  9. customcollecting all the eluent
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-f1249ce3ac804072b7cab113e4a553ad
Source dataset
uspto-grants-2013_11
Patent number
US08575340B2

Reaction notes

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