N,N-Dimethylaniline → HCID 11251187, compound

HRID 2114172Notes

Reaction equation

HRID 2114172 reaction equation
[OH:1][CH2:2][C:3]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].CN(C)C1C=CC=CC=1.ClC(Cl)(O[C:33](=[O:39])[O:34][C:35](Cl)(Cl)Cl)Cl.[CH3:41][N:42]([CH3:72])[C:43]([C:45]1[CH:50]=C(O)[C:48]([F:52])=[CH:47][C:46]=1[NH:53][C:54]([C:56]1[C:57]([C:62]2[CH:67]=[CH:66][C:65]([C:68]([F:71])([F:70])[F:69])=[CH:64][CH:63]=2)=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:55])=[O:44]>C(Cl)(Cl)Cl.C1COCC1.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:12]([O:11][C:9](=[O:10])[C:3]([CH2:2][O:1][C:33]([O:34][C:35]1[CH:50]=[C:45]([C:43](=[O:44])[N:42]([CH3:72])[CH3:41])[C:46]([NH:53][C:54]([C:56]2[C:57]([C:62]3[CH:63]=[CH:64][C:65]([C:68]([F:69])([F:71])[F:70])=[CH:66][CH:67]=3)=[CH:58][CH:59]=[CH:60][CH:61]=2)=[O:55])=[CH:47][C:48]=1[F:52])=[O:39])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH3:13]

Participants

9

Reactant 4

HCID 949N,N-DimethylanilineHCID 94429TriphosgeneHCID 22236963Diethyl 2-(hydroxymethyl)-2-phenylmalonateHCID 58706399HCID 58706399, compound

Product 1

HCID 11251187HCID 11251187, compoundYield 44.2%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of diethyl 2-hydroxymethyl-2-phenylmalonate (179 mg) and N,N-dimethylaniline (122 mg) in chloroform was added triphosgene (80 mg) under ice-cooling, and the mixture was stirred at room temperature, and after 3 hours, added dropwise to a solution of 4′-trifluoromethylbiphenyl-2-carboxylic acid (2-dimethylcarbamoyl-5-fluoro-4-hydroxyphenyl)amide (200 mg) and triethylamine (68 mg) in THF under ice-cooling. The mixture was stirred at room temperature for 2 hours, and then diluted with ethyl acetate. The extract was washed successively with saturated aqueous sodium bicarbonate and saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 2-{5-dimethylcarbamoyl-2-fluoro-4-[(4′-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxycarbonyloxymethyl}-2-phenylmalonic acid diethyl ester (88 mg).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringThe mixture was stirred at room temperature for 2 hours
  4. washThe extract was washed successively with saturated aqueous sodium bicarbonate and saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-db1dd0b6aa1a4bf680dc4988bc563c5b
Source dataset
uspto-grants-2008_10
Patent number
US07432392B2

Reaction notes

Loading…