Hexane → 1-Benzyloxycarbonyl-3-[2-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]ethenyl]piperidine

HRID 602195Notes

Reaction equation

HRID 602195 reaction equation
C([Li])CCC.CCCCCC.[I-].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[S:21][C:22]([CH2:26][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[C:23]([CH3:25])[N:24]=2)=[CH:16][CH:15]=1.[CH2:46]([O:53][C:54]([N:56]1[CH2:61][CH2:60][CH2:59][CH:58]([CH:62]=O)[CH2:57]1)=[O:55])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>O1CCCC1.O>[CH2:46]([O:53][C:54]([N:56]1[CH2:61][CH2:60][CH2:59][CH:58]([CH:62]=[CH:26][C:22]2[S:21][C:20]([C:17]3[CH:16]=[CH:15][C:14]([Cl:13])=[CH:19][CH:18]=3)=[N:24][C:23]=2[CH3:25])[CH2:57]1)=[O:55])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 9899653Benzyl 3-formylpiperidine-1-carboxylateHCID 86615887[2-(4-Chlorophenyl)-4-methylthiazol-5-yl]methyltriphenylphosphonium iodideHCID 178418339Butyllithium

Product 1

HCID 672674511-Benzyloxycarbonyl-3-[2-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]ethenyl]piperidineYield 87.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

In an argon atmosphere, a solution of 1.59 mol/Ln-butyl lithium in hexane (2.03 mL, 3.23 mmol), chilled to −78° C., was added to a suspension of [2-(4-chlorophenyl)-4-methylthiazol-5-yl]methyltriphenylphosphonium iodide (1.80 g, 2.94 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred for 1 hour as it warmed from −78° C. to room temperature. Subsequently, the mixture was chilled again to −78° C. and 1-benzyloxycarbonyl-3-formylpiperidine (727 mg, 2.94 mmol) in tetrahydrofuran (5 mL) was added. The mixture was stirred at −78° C. for 1 hour and at room temperature for the subsequent 6 hours. Subsequently, water was added and the mixture was extracted with ethyl acetate and washed with brine. The washed product was dried over magnesium sulfate and the solvent was evaporated. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=20:1->5:1) gave 1.16 g (87%) of the desired compound as a yellow oil.

Workup

  1. temperaturewarmed from −78° C. to room temperature
  2. stirringThe mixture was stirred at −78° C. for 1 hour and at room temperature for the subsequent 6 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe washed product was dried over magnesium sulfate
  6. customthe solvent was evaporated
  7. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=20:1->5:1)

Sources & evidence

ORD record
ord-6120e0c8674240beb93610cabdc551eb
Source dataset
uspto-grants-2011_03
Patent number
US07902367B2

Reaction notes

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