Dichloromethane → HCID 57595393, compound

HRID 1785969Notes

Reaction equation

HRID 1785969 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C@H:18]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[CH2:17][C@@H:16]2[CH3:33])=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.C(Cl)Cl.[C:46](Cl)(=[O:48])[CH3:47]>>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:8]=1)[C:13]([N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@H:18]([N:25]([C:26]2[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[C:46](=[O:48])[CH3:47])[CH2:17][C@@H:16]1[CH3:33])=[O:14]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 57595399HCID 57595399, compound

Product 1

HCID 57595393HCID 57595393, compoundYield 86%

Procedure

A solution of (3,5-bis(trifluoromethyl)phenyl)((2S,4R)-4-(4-chlorophenylamino)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)methanone (19.44 g, 0.037 mol) in acetyl chloride (5 mL) was cooled to 0° C. and triethylamine (6.59 mL, 0.037 mol) was added dropwise over 30 min, a precipitate forms during this time. An additional 250 mL of methylene chloride was added to completely dissolve all the precipitate. The reaction was allowed to stir overnight at room temperature. The mixture was concentrated under reduced pressure, partitioned between ethyl acetate and 1N sodium hydroxide while cooled to 0° C. The aqueous layer was extracted 3 times with ethyl acetate washed with sat. aqueous sodium bicarbonate, brine and dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (25/75 hexanes/ethyl acetate gradient) to afford pure N-((2S,4R)-1-(3,5-bis(trifluoromethyl)benzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-(4-chlorophenyl)acetamide (H-31) (18.2 g, 86%).

Workup

  1. dissolutionto completely dissolve all the precipitate
  2. concentrationThe mixture was concentrated under reduced pressure
  3. custompartitioned between ethyl acetate and 1N sodium hydroxide
  4. temperaturewhile cooled to 0° C
  5. extractionThe aqueous layer was extracted 3 times with ethyl acetate
  6. washwashed with sat. aqueous sodium bicarbonate, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (25/75 hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-5398365646f94010a1d6ec6a5b5c7211
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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