2,2,6,6-Tetramethylpiperidine → HCID 57893694, compound

HRID 1821986Notes

Reaction equation

HRID 1821986 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[F:16][C:17]1[CH:30]=[CH:29][CH:28]=[CH:27][C:18]=1[O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1.[Br:31]C(Cl)(Cl)C(Br)(Cl)Cl>C1COCC1>[Br:31][C:30]1[C:17]([F:16])=[C:18]([CH:27]=[CH:28][CH:29]=1)[O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 45097170HCID 45097170, compoundHCID 178418339Butyllithium

Product 1

HCID 57893694HCID 57893694, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Add n-butyl lithium (1.6 M in hexane, 7.4 mL) to a solution of 2,2,6,6-tetramethyl-piperidine (1.67 g) in THF (30 mL) at −78° C. and stir. After 15 min., add dropwise a solution of 4-(2-fluoro-phenoxy)-1-methyl-piperidine preparation 17, 1.65 g) in THF (20 mL) and stir. After 1 hr., add dropwise 1,2-dibromo-1,1,2,2-tetrachloro-ethane (2.57 g) in THF (15 mL) and stir. After 30 min. at −78° C. and 1 hr. at room temperature, partition between ethyl acetate and saturated aqueous NaCl, dry over anhydrous sodium sulfate, evaporate and purify on a silica gel column (110 g, solvent: dichloromethane-2M NH3 in methanol, gradient) to give the title compound (1.25 g). Mass spectrum (electric spray) m/z=288 (M+1), 290 (M+2+1); 1H NMR (CDCl3): 7.12 (m, 1H), 6.92 (m, 2H), 4.30 (m, 1H), 2.69 (m, 2H), 2.30 (s, 3H), 2.28 (m, 2H), 1.97 (m, 2H), 1.89 (m, 2H).

Workup

  1. additionadd dropwise
  2. stirringstir
  3. waitAfter 1 hr
  4. stirringstir
  5. waitAfter 30 min. at −78° C.
  6. custom1 hr
  7. customat room temperature, partition between ethyl acetate and saturated aqueous NaCl
  8. dry with materialdry over anhydrous sodium sulfate
  9. customevaporate
  10. custompurify on a silica gel column (110 g, solvent: dichloromethane-2M NH3 in methanol, gradient)

Sources & evidence

ORD record
ord-298ab7a61521418cbe13903df384632c
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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