Dibromomethane → tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(1-naphthalen-2-yl-vinyloxy)-piperidine-1-carboxylate

HRID 1005092Notes

Reaction equation

HRID 1005092 reaction equation
[CH3:1]N(C)CCN(C)C.BrCBr.[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]2[O:32][C:33]([C:35]2[CH:44]=[CH:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]=2)=O)=[CH:15][CH:14]=1.[Cl-].[NH4+]>C(Cl)Cl.O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.[Zn]>[F:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH2:21][CH:20]2[O:32][C:33]([C:35]2[CH:44]=[CH:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]=2)=[CH2:1])=[CH:17][CH:18]=1

Participants

9

Reactant 4

HCID 3024DibromomethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 54107379tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(naphthalen-2-ylcarbonyloxy)-piperidine-1-carboxylate

Product 1

HCID 53663664tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(1-naphthalen-2-yl-vinyloxy)-piperidine-1-carboxylateYield 46%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2.7 ml (24.6 mmol) of titanium tetrachloride in 18 ml of methylene chloride was added dropwise at 0° C. under argon and with the exclusion of moisture to 30 ml of tetrahydrofuran, a yellow suspension resulting. After warming to room temperature 15 ml (95 mmol) of tetramethylethylenediamine were added and the reaction mixture was stirred for 10 minutes. After the addition of 3.6 g (55 mmol) of zinc dust the mixture was stirred at room temperature for a further 30 minutes. Thereupon, a solution of 2.1 ml (30 mmol) of dibromomethane and 2.7 g (6.0 mmol) of tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(naphthalen-2-ylcarbonyloxy)-piperidine-1-carboxylate dissolved in 30 ml of tetrahydrofuran was added dropwise in such a manner that the temperature did not rise above 36° C. Subsequently, the reaction mixture was stirred at room temperature for 60 hours, then poured into saturated ammonium chloride solution and extracted with ether. The combined ether phases were dried over magnesium sulphate, concentrated and the residue was chromatographed on silica gel using a 99:1 mixture of methylene chloride and triethylamine as the eluent. Therefrom there were obtained 1.23 g (46% of theory) of tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(1-naphthalen-2-yl-vinyloxy)-piperidine-1-carboxylate as an amorphous colourless solid; MS: 448 (M+H)+.

Workup

  1. customa yellow suspension resulting
  2. additionwere added
  3. stirringwas stirred at room temperature for a further 30 minutes
  4. additionwas added dropwise in such a manner that the temperature
  5. customdid not rise above 36° C
  6. stirringSubsequently, the reaction mixture was stirred at room temperature for 60 hours
  7. extractionextracted with ether
  8. dry with materialThe combined ether phases were dried over magnesium sulphate
  9. concentrationconcentrated
  10. customthe residue was chromatographed on silica gel using
  11. additiona 99:1 mixture of methylene chloride and triethylamine as the eluent

Sources & evidence

ORD record
ord-d024b39b0e7a423b9879b4859712da34
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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