Tetrahydrofuran → HCID 68503586, compound

HRID 1710665Notes

Reaction equation

HRID 1710665 reaction equation
[Mg].Br[C:3]1[CH:4]=[CH:5][C:6]([Cl:11])=[C:7]([O:9][CH3:10])[CH:8]=1.[C:12]([N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C:20]1=O)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C1C[O:29]CC1>>[C:15]([O:14][C:12]([N:19]1[CH2:24][CH2:23][C:22]([C:3]2[CH:4]=[CH:5][C:6]([Cl:11])=[C:7]([O:9][CH3:10])[CH:8]=2)([OH:29])[CH2:21][CH2:20]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 27695675-Bromo-2-chloroanisoleHCID 5462224MagnesiumHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylate

Product 1

HCID 68503586HCID 68503586, compound

Conditions

Temperature
0 °C

Procedure

Magnesium turnings (2.60 g) in a flask were stirred vigorously under vacuum at room temperature for 12 h and then the flask was filled with nitrogen gas. THF (20 mL) was added followed by the addition of one crystal of 12. The mixture was cooled to 0° C. and a solution of 5-bromo-2-chloroanisole (6.64 g) in THF (100 mL) was added in a period of 10 min. The mixture was warmed up to room temperature and stirred at room temperature for 15 min before it was heated to 45° C. for 2 h to provide a solution of the Grignard solution. To 24 mL of the Grignard solution obtained from above (at −40° C.) was added N-Boc-piperidone (1.0 g) in one portion. The resultant mixture was warmed up to room temperature, stirred for 1 h and quenched by the addition of sat. aqueous NH4Cl solution (20 mL). The organic layer was separated and the aqueous layer was extracted by EtOAc (3×20 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was purified by flash chromatography to provide 4-(4-Chloro-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil (502 mg).

Workup

  1. additionthe flask was filled with nitrogen gas
  2. temperatureThe mixture was warmed up to room temperature
  3. temperaturewas heated to 45° C. for 2 h
  4. customto provide a solution of the Grignard solution
  5. customTo 24 mL of the Grignard solution obtained from above (at −40° C.)
  6. stirringstirred for 1 h
  7. customquenched by the addition of sat. aqueous NH4Cl solution (20 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted by EtOAc (3×20 mL)
  10. dry with materialThe combined organic layers were dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe crude residue was purified by flash chromatography

Sources & evidence

ORD record
ord-9593eca46c014105bdcf6d8492ab93b0
Source dataset
uspto-grants-2010_09
Patent number
US07790726B2

Reaction notes

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