2,6-Difluorophenyl isocyanate → HCID 86686923, compound

HRID 2363885Notes

Reaction equation

HRID 2363885 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1.[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=1[N:32]=[C:33]=[O:34]>C(Cl)Cl.O>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:17][CH2:18][N:19]([C:33](=[O:34])[NH:32][C:26]3[C:27]([F:31])=[CH:28][CH:29]=[CH:30][C:25]=3[F:24])[CH2:20][CH2:21]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1

Participants

5

Reactant 2

HCID 5221622,6-Difluorophenyl isocyanateHCID 86686890HCID 86686890, compound

Product 1

HCID 86686923HCID 86686923, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (6-fluoro-3-methyl-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester (which may be prepared as described above; 75.5 mg, 0.239 mmol) in methylene chloride (8.0 mL) was added neat 2,6-difluorophenyl isocyanate (74.1 mg, 0.478 mmol) at room temperature under nitrogen. The resulting light brown solution was stirred overnight. The reaction mixture was diluted with water (˜20 mL) and the resulting mixture was extracted with methylene chloride (2×30 mL). The combined organic layers were washed with saturated aqueous NaHCO3, dried over anhydrous Na2SO4, filtered, then concentrated to a yellowish film. Silica gel chromatography (33% ethyl acetate in hexanes) provided {4-[1-(2,6-difluoro-phenylcarbamoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (95.4 mg, 85%) as a colorless film. MS cald. for C26H26F3N2O3 [(M+H)+]: 471, obsd. 471.2.

Workup

  1. extractionthe resulting mixture was extracted with methylene chloride (2×30 mL)
  2. washThe combined organic layers were washed with saturated aqueous NaHCO3
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to a yellowish film

Sources & evidence

ORD record
ord-cb4418e956ea4bc4ad34a639a9350bc9
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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