2,4-Dichlorobenzoyl chloride → HCID 86686920, compound

HRID 2363880Notes

Reaction equation

HRID 2363880 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.[Cl:24][C:25]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28].C(N(CC)C(C)C)(C)C>ClCCl.O.[Cl-].[Na+].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:27](=[O:28])[C:26]3[CH:30]=[CH:31][C:32]([Cl:34])=[CH:33][C:25]=3[Cl: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

7

Reactant 3

HCID 666452,4-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 86686890HCID 86686890, compound

Product 1

HCID 86686920HCID 86686920, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a light brown solution of (6-fluoro-3-methyl-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester (which may be prepared as described above; 110 mg, 0.35 mmol) and 2,4-dichlorobenzoyl chloride (110 mg, 0.53 mmol) in dichloromethane (10 mL) was added N,N-diisopropylethylamine (183 μL, 1.05 mmol) at room temperature under a nitrogen atmosphere. The resulting light brown solution was stirred for 15 hours. The reaction mixture was diluted with water and brine and the resulting mixture was extracted into ethyl acetate (2×50 mL). The combined organic extracts were washed with brine solution, dried over MgSO4, filtered, and concentrated to give the crude product. Flash chromatography (40 g ISCO column, eluting with 0-60% ethyl acetate/hexanes) provided {4-[1-(2,4-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (111 mg, 65%) as a white solid. MS cald. for C26H25Cl2FNO3 [(M+H)−] 488, obsd. 488.0.

Workup

  1. extractionthe resulting mixture was extracted into ethyl acetate (2×50 mL)
  2. washThe combined organic extracts were washed with brine solution
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. washFlash chromatography (40 g ISCO column, eluting with 0-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7599277a18ea4ee98bfdb38ad8d7a000
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

Loading…