Iodine → HCID 68503586, compound

HRID 2104235Notes

Reaction equation

HRID 2104235 reaction equation
[Mg].II.Br[C:5]1[CH:6]=[CH:7][C:8]([Cl:13])=[C:9]([O:11][CH3:12])[CH:10]=1.[C:14]([N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C:22]1=O)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C1C[O:31]CC1>>[C:17]([O:16][C:14]([N:21]1[CH2:26][CH2:25][C:24]([C:5]2[CH:6]=[CH:7][C:8]([Cl:13])=[C:9]([O:11][CH3:12])[CH:10]=2)([OH:31])[CH2:23][CH2:22]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 5

HCID 807IodineHCID 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 I2. 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 20 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-85682aebadbf438ba73b40edba3c6a21
Source dataset
uspto-grants-2009_08
Patent number
US07576218B2

Reaction notes

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