Triethylamine → 2-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamide

HRID 1446700ノート

反応式

HRID 1446700 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([F:12])[CH:3]=1.Cl.CN(C)CCCN=C=NCC.[NH2:25][C:26]1[CH:27]=[C:28]([C:36]([N:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)=[O:37])[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:25][C:26]2[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[C:28]([C:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[O:37])[CH:27]=2)=[O:11])=[C:4]([F:12])[CH:3]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 66876746Morpholine, 4-[3-amino-5-(trifluoromethyl)benzoyl]-

生成物 1

HCID 685434652-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamide収率 15%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Dissolve (4-bromo-2-fluoro-phenyl)-acetic acid (692 mg, 3.0 mmol) in THF (24 mL) and add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (618 mg, 3.2 mmol), stir for 10 minutes. Dissolve (3-amino-5-trifluoromethyl-phenyl)-morpholin-4-yl-methanone (740 mg, excluding excess ammonium chloride) from previous step in DCM (24 mL) with Et3N (3.3 mL, 23 mmol). Add the activated acid to the amine mixture and stir at room temperature for overnight. Dilute the resulting suspension with EtOAc and wash with saturated NaHCO3 and aqueous saturated sodium chloride successively. Dry the organic layer (MgSO4), concentrate and purify by silica gel column chromatography (EtOAc/Hexane gradient) to obtain the title compound (15% yield). LCMS (ES), m/z 491 (M+1).

後処理

  1. stirringstir at room temperature for overnight
  2. washwash with saturated NaHCO3 and aqueous saturated sodium chloride successively
  3. dry with materialDry the organic layer (MgSO4)
  4. concentrationconcentrate
  5. custompurify by silica gel column chromatography (EtOAc/Hexane gradient)

出典と根拠

ORDレコード
ord-c5e2c30bf045471c93be85cef0b8f2b5
出典データセット
uspto-grants-2010_02
特許番号
US07666879B2

反応ノート

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