4-Methylpiperidine → HCID 58754821, compound

HRID 1711268Notes

Reaction equation

HRID 1711268 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-])=O.[CH3:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[K+].[C:43]([C:45]1[N:46]=[C:47]([C:58]([O-])=[O:59])[N:48]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:49]=1)#[N:44].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.C1COCC1>[CH3:11][CH:12]1[CH2:17][CH2:16][N:15]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[NH:8][C:58]([C:47]2[N:48]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:49]=[C:45]([C:43]#[N:44])[N:46]=2)=[O:59])[CH2:14][CH2:13]1

Participants

9

Reactant 5

HCID 693814-MethylpiperidineHCID 738951-Fluoro-2-nitrobenzeneHCID 81531Diisopropylethylamine2×HCID 2733179PyBroP2×HCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate2×

Product 1

HCID 58754821HCID 58754821, compoundYield 355.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 1.00 g (7.09 mmol) of 1-fluoro-2-nitro-benzene in DMF (5 mL) was treated with 2.52 mL (21.3 mmol) of 4-methyl-piperidine and heated to 60° C. for 15 min. The mixture was diluted with EtOAc (50 mL) and washed with water (6×30 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. A 250 mg (1.14 mmol) portion of the residue was taken up in THF (5 mL) and treated with 15 mg of 10% Pd/C (Degussa type E101-NE/W, Aldrich, 50% by weight water) under H2 (1 atm). When this reaction was complete, the mixture was filtered through Celite directly into a suspension of 24.5 mg (0.147 mmol) of PyBroP, 30.0 mg (0.0980 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 11, step (d)), and 51.0 μL (0.295 mmol) of DIEA in THF (5 mL). The mixture was flushed with Ar and stirred at RT for 16 h. An additional 24.5 mg (0.147 mmol) of PyBroP, 30.0 mg (0.0980 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 11, step (d)), and 51.0 μL (0.295 mmol) of DIEA were added, and the mixture stirred for 2 h. The mixture was diluted with EtOAc (10 mL), washed with water (1×10 mL) and saturated aqueous NaHCO3 (1×10 mL), dried (MgSO4), and concentrated in vacuo to afford 153 mg (30%) of the title compound as a white solid: Mass spectrum (ESI, m/z): Calcd. for C23H33N5Si, 440.2 (M+H), found 440.0.

Workup

  1. washwashed with water (6×30 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. additiontreated with 15 mg of 10% Pd/C (Degussa type E101-NE/W, Aldrich, 50% by weight water) under H2 (1 atm)
  5. customThe mixture was flushed with Ar
  6. stirringthe mixture stirred for 2 h
  7. washwashed with water (1×10 mL) and saturated aqueous NaHCO3 (1×10 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9cd192cc8ed04875a3fd264b0b60364b
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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