Cyclohexane → (S)-tert-Butyl 3-(bromomethyl)piperidine-1-carboxylate

HRID 1864000Notes

Reaction equation

HRID 1864000 reaction equation
O[CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1CCCCC1>C(Cl)Cl>[Br:17][CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

Participants

6

Reactant 4

HCID 8078CyclohexaneHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 1514448tert-Butyl (3S)-3-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 34177035(S)-tert-Butyl 3-(bromomethyl)piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1,1-dimethylethyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate (30.0 g, 139 mmol) and carbon tetrabromide (72.0 g, 217 mmol) in methylene chloride (150 mL) was added dropwise a solution of triphenyl phosphine (42.4 g, 162 mmol) in methylene chloride (150 mL). An ice-bath was used to maintain an internal temperature between 20 and 25° C. during the addition. After stirring the mixture at ambient temperature for 1 h, cyclohexane (500 mL) was added. Approximately one-half of the solvent was removed under reduced pressure. The remaining solution was cooled in an ice bath and the resulting precipitate was removed by filtration. The filtrate was concentrated under reduced pressure and the residue subjected to flash chromatography (0% to 25% ethyl acetate/hexanes, silica gel) to give 35.1 g (91% yield) of the desired product as a solid. MS (ES+) m/z 278 (M+H)+.

Workup

  1. customAn ice-bath was used
  2. temperatureto maintain an internal temperature between 20 and 25° C.
  3. additionduring the addition
  4. customApproximately one-half of the solvent was removed under reduced pressure
  5. temperatureThe remaining solution was cooled in an ice bath
  6. customthe resulting precipitate was removed by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6649e41ae8554d88b45db195e9a9556a
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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