Trichloroacetonitrile → 3-chloro-4-[(3,4-dimethoxyphenyl)methoxy]-N-methyl-N-[2-[[(1-methylethyl)amino]carbonyl]-4-phenoxyphenyl]-benzamide

HRID 2099979Notes

Reaction equation

HRID 2099979 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=1[Cl:17].ClC(Cl)(Cl)C#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:48]([NH:51][C:52](=[O:68])[C:53]1[CH:58]=[C:57]([O:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:56]=[CH:55][C:54]=1[NH:66][CH3:67])([CH3:50])[CH3:49]>C(Cl)Cl.C1COCC1>[Cl:17][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:8]=1[O:7][CH2:6][C:5]1[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:3]([O:2][CH3:1])[CH:4]=1)[C:12]([N:66]([CH3:67])[C:54]1[CH:55]=[CH:56][C:57]([O:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[CH:58][C:53]=1[C:52]([NH:51][CH:48]([CH3:49])[CH3:50])=[O:68])=[O:14]

Participants

7

Reactant 4

HCID 11011Trichloroacetonitrile2×HCID 11776Triphenylphosphine2×HCID 57796896N-isopropyl-2-(methylamino)-5-phenoxybenzamideHCID 577968974-(3,4-Dimethoxybenzyloxy)-3-chlorobenzoic acid

Product 1

HCID 577968883-chloro-4-[(3,4-dimethoxyphenyl)methoxy]-N-methyl-N-[2-[[(1-methylethyl)amino]carbonyl]-4-phenoxyphenyl]-benzamideYield 87.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A slurry of 1B (28 mg, 0.09 mmol) and trichloroacetonitrile (0.009 mL, 0.09 mmol) in CH2Cl2 (1 mL) at room temperature was treated with a solution of triphenylphosphine (22 mg, 0.09 mmol) in THF (0.25 mL). The reaction mixture was stirred for 30 minutes and additional trichloroacetonitrile (0.009 mL, 0.09 mmol) and triphenylphosphine (22 mg, 0.09 mmol) were added. The resulting solution was treated with 44B (16 mg, 0.06 mmol) in CH2Cl2 (0.5 mL). The stirring was continued for 2 hours, and then the reaction concentrated to dryness. The residue was purified by chromatography (SiO2, 50% to 75% EtOAc in hexanes) to afford 44C (31 mg).

Workup

  1. waitThe stirring was continued for 2 hours
  2. concentrationthe reaction concentrated to dryness
  3. customThe residue was purified by chromatography (SiO2, 50% to 75% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2c90fc973cc74432bb313e260acb7af5
Source dataset
uspto-grants-2009_08
Patent number
US07569725B2

Reaction notes

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