Triethylamine → Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

HRID 1466450ノート

反応式

HRID 1466450 の反応式
Cl.[NH2:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)=[CH:25][C:24]=1[CH2:36][C:37](O)=[O:38].P(Cl)(Cl)(Cl)=O>O1CCCC1>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)=[CH:25][C:24]=1[CH2:36][C:37]([NH:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1)=[O:38]

参加物

6

反応物 4

HCID 8471Triethylamine2 回HCID 24813Phosphorus oxychlorideHCID 60196672Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochlorideHCID 67372946(4,4'-Dichlorobiphenyl-3-yl)acetic acid

生成物 1

HCID 86707850Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

2.53 g (11 mmol) of the compound from Example 4A were initially charged in 50 ml of absolute tetrahydrofuran (THF). 3.07 ml of triethylamine were added dropwise at 20° C., the mixture was stirred for 5 min, and 2.81 g (10 mmol) of (4,4′-dichlorobiphenyl-3-yl)acetic acid (EP 1943218 A1 and US 2009/215624 A1) were added. After 15 min, a further 2.3 ml of triethylamine were added, followed immediately by the dropwise addition of 0.58 ml (6.2 mmol) of phosphorus oxychloride, and the mixture was stirred under reflux for 30 min. The mixture was concentrated under reduced pressure and the residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1. This gave 3.3 g (59% of theory) of the title compound of melting point 146-147° C.

後処理

  1. waitAfter 15 min
  2. stirringthe mixture was stirred
  3. temperatureunder reflux for 30 min
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1

出典と根拠

ORDレコード
ord-187b1c4383c34993b8ae21a9b59c1cbf
出典データセット
uspto-grants-2015_04
特許番号
US09000026B2

反応ノート

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