2,2,6,6-Tetramethylpiperidine → HCID 66938504, compound

HRID 1716892Notes

Reaction equation

HRID 1716892 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[F:31])[CH2:19][CH2:18]1.[Br:32]C(Cl)(Cl)C(Br)(Cl)Cl>C1COCC1>[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Br:32])[C:26]=2[F:31])[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 781972N-[(2-fluorophenyl)methyl]-1-methylpiperidin-4-amineHCID 178418339Butyllithium

Product 1

HCID 66938504HCID 66938504, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Add n-butyl lithium (1.6 M in hexanes, 4.3 mL) into a solution of 2,2,6,6-tetramethyl-piperidine (0.97 g) in THF (10 mL) at −78° C. and stir for 30 minutes. Add a solution of 1-methyl-4-(N-(2-fluorophenyl)methylamino)piperidine (Preparation 23, 1.02 g) in THF (10 mL) portion wise and stir for 10 minutes. Add 1,2-dibromo-1,1,2,2-tetrachloroethane (1.50 g) in THF (10 mL) dropwise and stir for 1 hr. Remove the cooling bath and stir for 30 minutes. Partition between ethyl acetate and saturated aqueous NaCl, dry over anhydrous sodium sulfate, evaporate and purify on a silica gel column (110 g), using a gradient of dichloromethane-2M NH3 in methanol to give 0.49 g of the title intermediate.

Workup

  1. stirringstir for 10 minutes
  2. customRemove the cooling bath
  3. stirringstir for 30 minutes
  4. customPartition between ethyl acetate and saturated aqueous NaCl
  5. dry with materialdry over anhydrous sodium sulfate
  6. customevaporate
  7. custompurify on a silica gel column (110 g)

Sources & evidence

ORD record
ord-b94a9e40c0d7401b936318919a0eb044
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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