4-Methylmorpholine → [1-(2-Phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester

HRID 242778

反応式

HRID 242778 の反応式
[C:1]1([NH:7][C:8]2[C:9]([NH2:14])=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([O:19][C:20]([NH:22][CH:23]([CH3:27])[C:24](O)=[O:25])=[O:21])([CH3:18])([CH3:17])[CH3:16].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[C:15]([O:19][C:20](=[O:21])[NH:22][CH:23]([C:24](=[O:25])[NH:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[NH:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH3:27])([CH3:16])([CH3:17])[CH3:18]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 68297N-Phenyl-o-phenylenediamineHCID 757711-HydroxybenzotriazoleHCID 2684712-N-Boc-aminopropionic acid2 回HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回

生成物 1

HCID 68157449[1-(2-Phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester収率 86.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

N-Phenylbenzene-1,2-diamine (1.84 g, 0.01 mol), racemic (R/S)-2-tertbutoxycarbonylaminopropionic acid (1.89 g, 0.01 mol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.92 g), 4-methylmorpholine (1.0 g, 0.01 mol), HOBt (1.53 g, 0.01 mol) were suspended in THF (10 mL) under a nitrogen atmosphere. The resulting mixture was stirred for 12 h at RT. After this period of time, additional amounts of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (500 mg×3) and of (R/S)-2-tertbutoxycarbonylaminopropionic acid (500 mg) were added and the mixture was stirred for further 4 h. The reaction mixture was then partitioned between water and EtOAc. The organic layer was separated, dried (MgSO4) and concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC ISCO 24 g column, gradient 0-20% EtOAc in cyclohexane). The product containing fractions were combined and concentrated in vacuo affording [1-(2-Phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester as a white crystalline solid (3.07 g, 86%). LCMS: RT 3.61 min [M+H-tBu]+ 300.1.

後処理

  1. stirringthe mixture was stirred for further 4 h
  2. customThe reaction mixture was then partitioned between water and EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue was purified by column chromatography (Si—PCC ISCO 24 g column, gradient 0-20% EtOAc in cyclohexane)
  7. additionThe product containing fractions
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-be45b9672691469baf49983c9874d67e
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

関連ノート

読み込み中…