Water → Tert-butyl 4-(3,4-dichlorobenzoyl)piperidine-1-carboxylate

HRID 369925Notes

Reaction equation

HRID 369925 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B#B.[OH2:25]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:25])[C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 6328200Diboron2×HCID 22257741Tert-butyl 4-(3,4-dichlorobenzylidene)piperidine-1-carboxylate

Product 1

HCID 53945757Tert-butyl 4-(3,4-dichlorobenzoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature solution of 1-(tert-butoxycarbonyl)-4-(3,4-dichlorobenzylidene)piperidine (6.4 g, 18.7 mmol) in dry THF (100 mL) under argon was added diborane (22.4 ml, 1 M in THF, 22.4 mmol) and the reaction mixture was stirred for 3 h. Water (20 ml) was slowly added dropwise to kill excess diborane. Tetrahydrofuran was remove in vacuo and ether (200 mL) was added. The reaction mixture was cooled in an ice bath and Jones reagent (take 18.6 g sodium dichromate hydrate, 14 mL conc. sulfuric acid and add enough water to make 93 mL solution) was added dropwise at a rate such that the reaction temperature stayed at about 25° C. The orange solution was stirred at room temperature 2 h. The organic layer was separated and the aqueous layer was extracted twice with ether. The combined organic layers were washed twice with dilute aqueous potassium carbonate solution, dried over anhydrous magnesium sulfate, and the organics were removed. The crude reaction mixtures was flash chromatographed on flash silica gel with a gradient of 10% ethyl acetate/hexane through 15% ethyl acetate/hexane to give 4-(3,4-dichlorobenzoyl)piperidine-1-carboxylic acid tert-butyl ester (3.8 g, 10.6 mmol).

Workup

  1. customTetrahydrofuran was remove in vacuo and ether (200 mL)
  2. additionwas added
  3. temperatureThe reaction mixture was cooled in an ice bath
  4. additionJones reagent (take 18.6 g sodium dichromate hydrate, 14 mL conc. sulfuric acid and add enough water to make 93 mL solution) was added dropwise at a rate such that the reaction temperature
  5. customstayed at about 25° C
  6. stirringThe orange solution was stirred at room temperature 2 h
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted twice with ether
  9. washThe combined organic layers were washed twice with dilute aqueous potassium carbonate solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe organics were removed
  12. customThe crude reaction mixtures
  13. customchromatographed on flash silica gel with a gradient of 10% ethyl acetate/hexane through 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-bec30dd38547467c9743871dc743dbcb
Source dataset
uspto-grants-2000_10
Patent number
US06140344

Reaction notes

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