Diisopropylethylamine → Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate

HRID 1808997ノート

反応式

HRID 1808997 の反応式
[OH:1][C:2]1([CH:6]2[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][NH:4][CH2:3]1.[F:20][C:21]1[C:22]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])=[C:23]([CH:27]=[CH:28][C:29]=1[F:30])[C:24](F)=[O:25].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:15]([O:14][C:13](=[O:19])[NH:12][CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH:6]1[C:2]1([OH:1])[CH2:3][N:4]([C:24](=[O:25])[C:23]2[CH:27]=[CH:28][C:29]([F:30])=[C:21]([F:20])[C:22]=2[NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])[CH2:5]1)([CH3:16])([CH3:18])[CH3:17]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 67051547Tert-butyl 2-(3-hydroxyazetidin-3-yl)cyclohexylcarbamate

生成物 1

HCID 86621268Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of tert-butyl 2-(3-hydroxyazetidin-3-yl)cyclohexylcarbamate (181 mg, 0.669 mmol) and 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl fluoride (265 mg, 0.669 mmol), prepared using procedures similar to those described in Reference 1, in tetrahydrofuran (2.2 mL) was added N,N-diisopropylethylamine (110 μL) at room temperature. After an hour, the reaction mixture was heated to 50° C. and stirred for 45 minutes, at which time it was cooled to room temperature and evaporated. The residue was partitioned between ethyl acetate and 10% citric acid. The organic layer was washed with aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate. This crude material was taken into the next step without further purification.

後処理

  1. waitAfter an hour
  2. temperaturewas cooled to room temperature
  3. customevaporated
  4. customThe residue was partitioned between ethyl acetate and 10% citric acid
  5. washThe organic layer was washed with aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-50dd8d3bcf9c4f51961cf1a8a45933ed
出典データセット
uspto-grants-2013_01
特許番号
US08362002B2

反応ノート

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