Sodium Hydroxide → HCID 69516187, compound

HRID 1297213Notes

Reaction equation

HRID 1297213 reaction equation
[C:1]([N:20]1[N:24]=[N:23][C:22]([CH2:25][C:26]#[N:27])=[N:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C=O)CCCCC1.[OH-].[Na+].[I-].C[S+](C)(C)=O.[H-].[Na+].[CH:46]1([CH:52]=[C:53](C2N=NN(C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)N=2)C#N)[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>C1C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.CCOC(C)=O>[CH:46]1([CH:52]2[CH2:53][C:25]2([C:22]2[N:23]=[N:24][N:20]([C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:21]=2)[C:26]#[N:27])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1

Participants

11

Reactant 6

HCID 14798Sodium HydroxideHCID 16275CyclohexanecarboxaldehydeHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 58914637HCID 58914637, compoundHCID 69516184HCID 69516184, compound

Product 1

HCID 69516187HCID 69516187, compoundYield 89.4%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 241BenzeneSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2-trityl-2H-tetrazol-5-yl)-acetonitrile (1.0 g, 2.85 mmol) in 15 mL benzene was added cyclohexanecarboxaldehyde (0.38 mL, 3.13 mmol), 10 mL 10% NaOH (aq), and tetrabutylammonium bromide (50 mg). The mixture was stirred for 1 h, then poured into EtOAc. The phases were separated, and the organic phase dried (MgSO4) and concentrated. Meanwhile, to trimethylsulfoxonium iodide (0.75 g, 3.42 mmol) in 7.0 mL DMF was added sodium hydride (60% dispersion in mineral oil, 0.14 g, 3.42 mmol). The mixture was stirred for 30 min at which time a solution of crude 3-cyclohexyl-2-(2-trityl-2H-tetrazol-5-yl)-acrylonitrile 2 (ca. 2.8 mmol) in 5.0 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 (15→20% EtOAc/hexanes) provided 1.15 g (88%, two steps) of 2-cyclohexyl-1-(2-trityl-2H-tetrazol-5-yl)-cyclopropanecarbonitrile as a colorless foam. 1H NMR (CDCl3) δ 7.33 (m, 9H), 7.07 (m, 6H), 1.88 (dd, J=4.9, 8.8 Hz, 1H, cyclopropyl —CHH), 1.66-1.84 (m, 4H), 1.57 (dd, J=4.9, 7.7 Hz, 1H, cyclopropyl —CHH), 1.25 (m, 8H).

Workup

  1. customThe phases were separated
  2. dry with materialthe organic phase dried (MgSO4)
  3. concentrationconcentrated
  4. additionwas added quickly dropwise
  5. stirringThe orange solution was stirred overnight
  6. custompartitioned between EtOAc and H2O
  7. customthe phases separated
  8. washThe organic phase was washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f213cf0fa26f4df28c2bcb771a2f51ee
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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