Triethylamine → (2'-{[Benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

HRID 2197343ノート

反応式

HRID 2197343 の反応式
[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:8]([F:11])=[CH:9][CH:10]=1.Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32].C(N(CC)CC)C.[H-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][C:13]=2[CH2:22][N:23]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH2:24][C:25]([F:28])([F:26])[F:27])[C:8]([F:11])=[CH:9][CH:10]=1

参加物

8

反応物 4

HCID 8471Triethylamine2 回HCID 10387Benzyl chloroformate3 回HCID 24758Sodium hydrideHCID 86633170{6-Fluoro-2'-[(2,2,2-trifluoro-ethylamino)-methyl]-4'-trifluoromethyl-biphenyl-3-yl}acetic acid methyl ester

生成物 1

HCID 86633173(2'-{[Benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

{6-Fluoro-2′-[(2,2,2-trifluoro-ethylamino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid methyl ester (0.26 g, 0.62 mmol), benzyl chloroformate (0.13 mL, 0.93 mmol), and triethylamine (0.13 mL, 0.93 mmol) were combined in CH2Cl2 (2.1 mL), and the reaction was stirred at room temperature for 2 hours. Additional benzyl chloroformate (0.13 mL, 0.93 mmol), and triethylamine (0.13 mL, 0.93 mmol) were added, and the reaction was stirred for 1 hour. Starting material was still present, so an aqueous work-up was performed, and the residue was dissolved in DMF and cooled to 0° C. Sodium hydride (60% in mineral oil; 0.030 g, 0.75 mmol) was added, followed by benzyl chloroformate (0.13 mL, 0.93 mmol), and the reaction was stirred for 20 minutes. The mixture was worked up with CH2Cl2 and H2O, and the organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography to give (2′-{[benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester. The ester was hydrolyzed according to the procedure described in Example 17, Step 3.

後処理

  1. stirringthe reaction was stirred for 1 hour
  2. temperaturecooled to 0° C
  3. stirringthe reaction was stirred for 20 minutes
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-5e01fbb4269d4f59a31572ebbd352960
出典データセット
uspto-grants-2012_12
特許番号
US08338484B2

反応ノート

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