Bromochloromethane → tert-butyl4-(chloromethyl)-4-cyanopiperidine-1-carboxylate

HRID 845857Notes

Reaction equation

HRID 845857 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:26]#[N:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Br[CH2:29][Cl:30]>CCCCCC.O1CCCC1.O>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]([CH2:29][Cl:30])([C:26]#[N:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 4

HCID 6333BromochloromethaneHCID 7912DiisopropylamineHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 14204594tert-butyl4-(chloromethyl)-4-cyanopiperidine-1-carboxylateYield 108.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

A solution of 1.42M-BuLi in hexane (7.75 ml) was added dropwise to a stirred solution of diisopropylamine (1.1 g) in tetrahydrofuran (30 ml) at -50° under nitrogen. The solution was warmed to 0°, cooled to -65°, and a solution of 1-tert-butyloxycarbonyl-4-cyanopiperidine (2.1 g) in tetrahydrofuran (20 ml) added dropwise, such that the temperature remained below -65°. The mixture was warmed to ambient temperature, cooled to -65°, and added dropwise to a stirred solution of bromochloromethane (6.47 g), in tetrahydrofuran (10 ml) under nitrogen such that the temperature remained below -65°. The mixture was warmed to ambient temperature, poured into water (20 ml), and extracted with chloroform (3×100 ml). The chloroform extracts were washed with ice-cold 0.011M-potassium hydrogen sulphate solution (1000 ml) and saturated aqueous sodium hydrogen carbonate (100 ml), dried (MgSO4), and evaporated under reduced pressure to give an oil (2.8 g) which slowly crystallised. The solid was purified by trituration with hexane, chromatography (SiO2 ; Et2O) and recrystallisation from diethyl ether-hexane to give the title compound (1.02 g), m.p. 114.5°-115.5°.

Workup

  1. temperatureThe solution was warmed to 0°
  2. temperaturecooled to -65°
  3. customremained below -65°
  4. temperaturecooled to -65°
  5. customremained below -65°
  6. temperatureThe mixture was warmed to ambient temperature
  7. extractionextracted with chloroform (3×100 ml)
  8. washThe chloroform extracts were washed with ice-cold 0.011M-potassium hydrogen sulphate solution (1000 ml) and saturated aqueous sodium hydrogen carbonate (100 ml)
  9. dry with materialdried (MgSO4)
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2c2ab76e314a425eadb1e84ae25ef378
Source dataset
uspto-grants-1988_07
Patent number
US04760158

Reaction notes

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