Cyclohexanone → HCID 69516895, compound

HRID 1297215Notes

Reaction equation

HRID 1297215 reaction equation
[H-].[Na+].[C:3]([N:22]1[N:26]=[N:25][C:24]([CH2:27][C:28]#[N:29])=[N:23]1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(=O)CCCCC1.[I-].C[S+](C)(C)=O.[C:43]1(=[C:49](C2N=NN(C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)N=2)C#N)[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1>C1COCC1.CN(C=O)C>[C:3]([N:22]1[N:26]=[N:25][C:24]([C:27]2([C:28]#[N:29])[C:43]3([CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)[CH2:49]2)=[N:23]1)([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 7967CyclohexanoneHCID 24758Sodium hydride2×HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 58914637HCID 58914637, compoundHCID 69517783HCID 69517783, compound

Product 1

HCID 69516895HCID 69516895, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flask charged with dry sodium hydride (0.34 g, 14.1 mmol) was added (2-trityl-2H-tetrazol-5-yl)-acetonitrile (2.49 g, 7.10 mmol). The solids were swirled to mix, cooled to 0° C., and 25 mL THF was added quickly, resulting in vigorous H2 evolution and a bright yellow foam. The mixture was stirred at 0° C. for 5 min, at which time the ice bath was removed and stirring continued for 10 min. Cyclohexanone (0.81 mL, 7.80 mmol) in 10 mL THF was added quickly resulting in a clear orange solution. The mixture was stirred for 2 h, partitioned between EtOAc and sat. NH4Cl (aq), and the organic phase dried (MgSO4) and concentrated. Meanwhile, to trimethylsulfoxonium iodide (2.48 g, 11.2 mmol) in 25 mL DMF was added sodium hydride (60% dispersion in mineral oil, 0.45 g, 11.2 mmol). The mixture was stirred for 30 min at which time a suspension of crude cyclohexylidene-(2-trityl-2H-tetrazol-5-yl)-acetonitrile (ca. 7.5 mmol) in 15 mL DMF was added quickly dropwise. The orange solution was stirred overnight, partitioned between EtOAc and H2O, and the phases separated. The organic phase was washed with brine, dried (MgSO4) and concentrated. Flash chromatography of the residue (CH2Cl2) provided 2.43 g (77%, two steps) of 1-(2-trityl-2H-tetrazol-5-yl)-spiro[2.5]octane-1-carbonitrile as a colorless foam. 1H NMR (CDCl3) δ 7.32 (m, 9H), 7.08 (m, 6H), 1.99 (d, J=5.4 Hz, 1H, cyclopropyl —CHH), 1.80 (m, 2H), 1.72 (m, 2H), 1.59 (d, J=5.4 Hz, 1H, cyclopropyl —CHH), 1.51 (m, 1H), 1.41 (m, 1H), 1.29 (m, 3H), 1.09 (m, 2H), 0.83 (m, 1H).

Workup

  1. additionto mix
  2. customresulting in vigorous H2 evolution
  3. customwas removed
  4. customresulting in a clear orange solution
  5. stirringThe mixture was stirred for 2 h
  6. custompartitioned between EtOAc and sat. NH4Cl (aq)
  7. dry with materialthe organic phase dried (MgSO4)
  8. concentrationconcentrated
  9. stirringThe mixture was stirred for 30 min at which time
  10. additionwas added quickly dropwise
  11. stirringThe orange solution was stirred overnight
  12. custompartitioned between EtOAc and H2O
  13. customthe phases separated
  14. washThe organic phase was washed with brine
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-ec12d3f148c44b8eaecbae2161b23be0
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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