Trimethylphosphine → Triethyl [1-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

HRID 1946526ノート

反応式

HRID 1946526 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14](O)[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:4][CH:3]=1.[CH2:22]([O:24][C:25]([CH:27]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[O:26])[CH3:23].CP(C)C.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([C:27]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:25]([O:24][CH2:22][CH3:23])=[O:26])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 68983TrimethylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 80471Triethyl methanetricarboxylateHCID 584601861-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-ol

生成物 1

HCID 67434822Triethyl [1-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a stirred solution of Intermediate 58 (99 mg) and triethylmethanetricarboxylate (0.14 mL) in anhydrous Toluene (3 mL) and anhydrous Tetrahydrofuran (THF) (3.00 mL) under a nitrogen atmosphere was added trimethylphosphine, 1M in Toluene (0.650 mL). The reaction was then cooled to −78° C. and diisopropyl azodicarboxylate (0.13 mL) added dropwise via syringe over 1 min. The reaction was stirred at −78° C. under an atmosphere of nitrogen for 90 mins before being allowed to warm to ambient temperature and stirred for a further 1 h. The reaction was concentrated in vacuo. The residue was taken up in dichloromethane (40 mL) and washed with water (40 mL), dried (hydrophobic frit) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica using a 0-100% ethyl acetate-cyclohexane gradient. The appropriate fractions were combined and evaporated in vacuo to give the required product (139 mg). LC/MS MH+ 519, Rt 2.15 min (5 min run).

後処理

  1. temperatureto warm to ambient temperature
  2. stirringstirred for a further 1 h
  3. concentrationThe reaction was concentrated in vacuo
  4. washwashed with water (40 mL)
  5. customdried (hydrophobic frit)
  6. concentrationconcentrated in vacuo
  7. custompurified on silica using a 0-100% ethyl acetate-cyclohexane gradient
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-d16e091948794b63bb39a0f04595e5c2
出典データセット
uspto-grants-2013_03
特許番号
US08399444B2

反応ノート

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