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

HRID 1433084Notes

Reaction equation

HRID 1433084 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][Br:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (2.30 g, 10.7 mmol) and carbon tetrabromide (4.43 g, 13.4 mmol) in CH2Cl2 (40 mL) is cooled to 0° C. Triphenylphosphine (4.21 g, 16.0 mmol) is added and the reaction is stirred at 25° C. for 1 h. The reaction is concentrated and ether is added to the residue. The mixture is filtered and washed with ether. The filtrate is concentrated and purified by column chromatography (silica, 20% EtOAc/hexane) to provide 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester as a crystaline solid upon standing. Mp 48-50° C.; 1H NMR (300 MHz, CDCl3) δ 4.13 (bm, 2H), 3.29 (d, 2H), 2.70 (dd, 2H), 1.85-1.73 (m, 3H), 1.46 (s, 9H), 1.28-1.13 (m, 2H); MS (EI) 277 (M)+.

Workup

  1. concentrationThe reaction is concentrated
  2. additionether is added to the residue
  3. filtrationThe mixture is filtered
  4. washwashed with ether
  5. concentrationThe filtrate is concentrated
  6. custompurified by column chromatography (silica, 20% EtOAc/hexane)

Sources & evidence

ORD record
ord-92cbbf925f6c4d8c85cbdf5038c65056
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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