3-Iodotoluene → Rac-4-phenyl-8-(1-m-tolyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 914937Notes

Reaction equation

HRID 914937 reaction equation
I[C:2]1[CH:3]=[C:4]([CH3:8])[CH:5]=C[CH:7]=1.C([Mg]Cl)(C)C.[O:14]=[C:15]1[C:19]2([CH2:24][CH2:23][N:22]([C:25]3([C:31]#N)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:20]2)[CH:18]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:17][NH:16]1>C1COCC1>[C:33]1([CH:18]2[C:19]3([CH2:24][CH2:23][N:22]([C:25]4([C:31]5[CH:5]=[C:4]([CH3:8])[CH:3]=[CH:2][CH:7]=5)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]4)[CH2:21][CH2:20]3)[C:15](=[O:14])[NH:16][CH2:17]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 122683-IodotolueneHCID 69486548Rac-1-(1-oxo-4-phenyl-2,8-diaza-spiro [4.5]dec-8-yl)-cyclohexanecarbonitrileHCID 178418918HCID 178418918, compound

Product 1

HCID 11373041Rac-4-phenyl-8-(1-m-tolyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-iodotoluene (388 mg, 1.8 mmol) in dry THF (6 mL) under argon at -60° C. was added isopropylmagnesium chloride (2 M solution in THF, 977 μL, 2.0 mmol) and the resulting solution allowed to warm up to 0° C. over 1 h and then to room temperature over 10 min. The resulting solution was then added dropwise to a solution of rac-1-(1-oxo-4-phenyl-2,8-diaza-spiro[4.5]dec-8-yl)-cyclohexanecarbonitrile (200 mg, 0.6 mmol) in dry THF (3 mL) and the solution stirred overnight at room temperature. The reaction was quenched by the addition of ammonium chloride solution (sat., 10 mL) and the product extracted with ethyl acetate (2×20 mL). The combined organic extracts were then washed with brine (20 mL), dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel eluting with DCM:MeOH:NH4OH (95:4.5:0.5) to afford the title compound (170 mg, 71%) as a white solid. MS: m/e=403.6 (M+H).

Workup

  1. customThe reaction was quenched by the addition of ammonium chloride solution (sat., 10 mL)
  2. extractionthe product extracted with ethyl acetate (2×20 mL)
  3. washThe combined organic extracts were then washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel eluting with DCM:MeOH:NH4OH (95:4.5:0.5)

Sources & evidence

ORD record
ord-92db3e2d0d5d4ccc98a7ef3095417625
Source dataset
uspto-grants-2007_09
Patent number
US07265126B2

Reaction notes

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