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4-Methylmorpholine → cis-3-(4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl ester

HRID 1669309
ノート
印刷プレビュー

反応式

HRID 1669309 の反応式
[F:1][C:2]([F:34])([F:33])[CH2:3][CH2:4][CH:5]([C:17]1[CH:18]=[N:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)=[CH:21][CH:22]=1)/[CH:6]=[CH:7]\[C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][CH:9]=1.Cl[C:36]1[C:37]([O:44][CH3:45])=NN=[N:40][C:41]=1OC.CN1CC[O:50]CC1.Cl.NCCC(O)=O>C(Cl)Cl.O>[CH3:45][O:44][C:37](=[O:50])[CH2:36][CH2:41][NH:40][C:12](=[O:13])[C:11]1[CH:15]=[CH:16][C:8](/[CH:7]=[CH:6]\[CH:5]([C:17]2[CH:18]=[N:19][C:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=3)=[CH:21][CH:22]=2)[CH2:4][CH2:3][C:2]([F:1])([F:33])[F:34])=[CH:9][CH:10]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 79724-Methylmorpholine2 回HCID 12201475beta-Alanine HydrochlorideHCID 12493616Chloro-dimethoxy-triazineHCID 86620359Cis-4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid

生成物 1

HCID 86620361cis-3-(4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl ester
収率 78%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

The cis-4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid (214 mg, 0.45 mmol), chloro-dimethoxy-triazine (CDMT) (81 mg, 0.46 mmol), and 4-methylmorpholine (50 uL, 0.47 mmol) are combined in anhydrous DCM under nitrogen. The reaction is allowed to stir under nitrogen at room temperature overnight. Beta-alanine hydrochloride (68 mg, 0.49 mmol) and 4-methylmorpholine (100 uL, 0.94 mmol) is then added to the reaction mixture, and allowed to stir at room temperature. Some water (<10% volume) is added to help solubility. The reaction is monitored by HPLC, and upon complete consumption of the acid, the reaction is diluted with DCM and water and rinsed with 1N HCl. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, then filtered and concentrated. The cis-3-(4-{6,6,6-trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl ester (197 mg, 0.35 mmol) is isolated after column chromatography, 78% yield.

後処理

  1. stirringto stir at room temperature
  2. customupon complete consumption of the acid
  3. additionthe reaction is diluted with DCM and water
  4. washrinsed with 1N HCl
  5. washThe organic layer is washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-0c95d264155e4ba3b071f18826fcb363
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07989457B2

反応ノート

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