Tetrahydrofuran → HCID 59865005, compound

HRID 1669743Notes

Reaction equation

HRID 1669743 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH2:15][C:14]([CH3:19])([CH3:18])[CH2:13]2)=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[C:25]([N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][C:33]1=O)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].[Cl-].[NH4+].C1C[O:44]CC1>C(OCC)(=O)C>[CH3:18][C:14]1([CH3:19])[CH2:15][CH2:16][CH2:17][N:12]([CH2:11][CH2:10][CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([C:35]3([OH:44])[CH2:36][CH2:37][N:32]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:33][CH2:34]3)=[CH:3][CH:4]=2)[CH2:13]1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 59865001HCID 59865001, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 59865005HCID 59865005, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

A solution of 1-{3-[(4-iodophenyl)oxy]propyl}-3,3-dimethylpiperidine (25 g) in THF (125 ml) is stirred for about 15 min, then cooled to 0-5° C. Isopropyl magnesium chloride solution (70.5 ml, 1.9M) is added at 0-5° C. over about 40 min, then the mixture is stirred at 0-5° C. for 2-3 h. The mixture is then cooled to −78 to −80° C. and a precooled solution (−20 to −30° C.) of N-Boc-piperidinone (16 g) in THF (125 ml) is added over about 1-2 h and the reaction mixture is stirred for about 1.5 h at −78 to −80° C. The reaction mixture is allowed to warm to 25-30° C., then stirred for 23-24 h. Saturated ammonium chloride solution (375 ml) is added at 25-30° C., followed by ethyl acetate (500 ml) and the mixture stirred for about 50 min. The aqueous layer is extracted with ethyl acetate (250 ml). The combined organic layers are washed with water (375 ml), dried over sodium sulfate and concentrated under reduced pressure to give the crude title compound (30.3 g).

Workup

  1. temperatureThe mixture is then cooled to −78 to −80° C.
  2. stirringthe reaction mixture is stirred for about 1.5 h at −78 to −80° C
  3. temperatureto warm to 25-30° C.
  4. stirringstirred for 23-24 h
  5. stirringthe mixture stirred for about 50 min
  6. extractionThe aqueous layer is extracted with ethyl acetate (250 ml)
  7. washThe combined organic layers are washed with water (375 ml)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-50fc68c6c393496ea348f08e7362dd7d
Source dataset
uspto-grants-2011_08
Patent number
US07989629B2

Reaction notes

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