Triethylamine → 6-{3-Chloro-4-[2-(4-cyano-3,5-dimethyl-phenyl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-4-trifluoromethyl-nicotinic acid methyl ester

HRID 2096854ノート

反応式

HRID 2096854 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:26])[C:10]([C:16]1[CH:23]=[C:22]([CH3:24])[C:19]([C:20]#[N:21])=[C:18]([CH3:25])[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:27][O:28][C:29](=[O:41])[C:30]1[C:35]([C:36]([F:39])([F:38])[F:37])=[CH:34][C:33](Cl)=[N:32][CH:31]=1.C(N(CC)CC)C.N12CCN(CC1)CC2>CN(C)C(=O)C.CCOC(C)=O.O>[CH3:27][O:28][C:29](=[O:41])[C:30]1[C:35]([C:36]([F:37])([F:38])[F:39])=[CH:34][C:33]([O:8][C:6]2[CH:5]=[CH:4][C:3]([CH:9]([CH3:26])[C:10]([C:16]3[CH:17]=[C:18]([CH3:25])[C:19]([C:20]#[N:21])=[C:22]([CH3:24])[CH:23]=3)([OH:15])[C:11]([F:14])([F:12])[F:13])=[C:2]([Cl:1])[CH:7]=2)=[N:32][CH:31]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 9237DabcoHCID 2775340Methyl 6-chloro-4-(trifluoromethyl)nicotinateHCID 666970264-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-2,6-dimethyl-benzonitrile

生成物 1

HCID 723101226-{3-Chloro-4-[2-(4-cyano-3,5-dimethyl-phenyl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-4-trifluoromethyl-nicotinic acid methyl ester収率 86.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of 4-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-2,6-dimethyl-benzonitrile (Example 141, step 5, 100 mg) in N,N-dimethylacetamide (1 ml) were added methyl-6-chloro-4-(trifluoromethyl)-nicotinate (75 mg), triethylamine (34 mg) and 1,4-diazabicyclo[2.2.2]octane (4 mg). The mixture was stirred at room temperature for 6 h and then diluted with EtOAc. Water was added. The mixture was extracted with EtOAc. The organic phase was washed with water, dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>2:3) to give the title compound (132 mg) as a colorless solid. MS (m/e, ISP neg. ion)=585.1 [M−H+].

後処理

  1. extractionThe mixture was extracted with EtOAc
  2. washThe organic phase was washed with water
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>2:3)

出典と根拠

ORDレコード
ord-5f7f3af30d0d45b3a3234b3bd58fbbf3
出典データセット
uspto-grants-2013_05
特許番号
US08450313B2

反応ノート

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