m-Methylphenylacetonitrile → HCID 22171052, compound

HRID 2376236Notes

Reaction equation

HRID 2376236 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[CH2:15][C:16]#[N:17].Br[CH2:22][C:23]1[CH:27]=[C:26]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)[N:25]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[N:24]=1>O1CCCC1>[Cl:35][C:30]1[CH:29]=[C:28]([C:26]2[N:25]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[N:24]=[C:23]([CH2:22][CH:15]([C:14]3[CH:13]=[C:12]([CH3:11])[CH:20]=[CH:19][CH:18]=3)[C:16]#[N:17])[CH:27]=2)[CH:33]=[CH:32][C:31]=1[Cl:34]

Participants

5

Reactant 3

HCID 76279m-MethylphenylacetonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 22171048HCID 22171048, compound

Product 1

HCID 22171052HCID 22171052, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of sodium bis(trimethylsilyl)amide (14.0 mL, 1.0 M solution in THF, 1.0 equiv) in tetrahydrofuran (56.0 mL) at 0° C. was added 3-methylbenzyl cyanide (1.84 g, 14.0 mmol, 1.0 equiv). This mixture was stirred at 0° C. for 30 min then was added to a solution of 3-bromomethyl-5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazole (prepared as in Method 1; 5.78 g, 14.0 mmol, 1.0 equiv) in tetrahydrofuran (56.0 mL) and allowed to stir for 2 h. The reaction was quenched with satd aq ammonium chloride (10.0 mL), and the resulting mixture was diluted with water (200 mL), and extracted with diethyl ether (2×100 mL). The combined extracts were dried (Na2SO4) and concentrated under reduced pressure. The crude material was purified by flash chromatography (25% ethyl acetate/hexanes) to yield the title intermediate (2.76 g, 43%). HPLC: Rt=13.44 (Method G). MS (ESI): mass calculated for C26H21Cl2N3O, 461.11; m/z found, 462.0 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.36 (d, J=1.9 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.28 (t, J=7.4 Hz, 1H), 7.24 (s, 1H), 7.23-7.21 (m, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.19-7.16 (m, 1H), 6.95 (dd, J=8.5, 2.2 Hz, 1H), 6.89 (d, J=8.8 Hz, 2H), 6.42 (s, 1H), 4.22 (dd, J=9.6, 6.0 Hz, 1H), 3.83 (s, 3H), 3.30-3.21 (m, 2H), 2.38 (s, 3H).

Workup

  1. stirringto stir for 2 h
  2. customThe reaction was quenched with satd aq ammonium chloride (10.0 mL)
  3. additionthe resulting mixture was diluted with water (200 mL)
  4. extractionextracted with diethyl ether (2×100 mL)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography (25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e69e5b5e2d244e478a2e3c1c919fbfae
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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