Chlorotrimethylsilane → Benzyl 3-(3-acetyl-5-chloro-2-ethoxy-6-methylphenyl)azetidine-1-carboxylate

HRID 1499716ノート

反応式

HRID 1499716 の反応式
BrCCBr.Cl[Si](C)(C)C.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:12]1.[Cl:25][C:26]1[C:27]([CH3:39])=[C:28](I)[C:29]([O:35][CH2:36][CH3:37])=[C:30]([C:32](=[O:34])[CH3:33])[CH:31]=1>CN(C)C=O.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>[C:32]([C:30]1[C:29]([O:35][CH2:36][CH3:37])=[C:28]([CH:11]2[CH2:14][N:13]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:12]2)[C:27]([CH3:39])=[C:26]([Cl:25])[CH:31]=1)(=[O:34])[CH3:33]

参加物

9

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 16244498Benzyl 3-iodoazetidine-1-carboxylateHCID 866668651-(5-Chloro-2-ethoxy-3-iodo-4-methylphenyl)ethanone

生成物 1

HCID 86666866Benzyl 3-(3-acetyl-5-chloro-2-ethoxy-6-methylphenyl)azetidine-1-carboxylate収率 80.2%

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 521585Tris(furan-2-yl)phosphane触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒3 回

反応条件

温度
70 °C

実験手順

Zinc (0.967 g, 14.8 mmol) was suspended with 1,2-dibromoethane (0.085 mL, 0.98 mmol) in N,N-dimethylformamide (17 mL). The mixture was heated at 70° C. for 10 minutes and then cooled to room temperature. Chlorotrimethylsilane (0.125 mL, 0.984 mmol) was added dropwise and stirring was continued for 1 hour. A solution of benzyl 3-iodoazetidine-1-carboxylate (from PharmaBlock) (3.9 g, 12 mmol) in N,N-dimethylformamide (10 mL) was then added and the mixture was heated at 40° C. for 1 hour before a mixture of 1-(5-chloro-2-ethoxy-3-iodo-4-methylphenyl)ethanone (4.4 g, 13 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.22 g, 0.24 mmol) and tri-(2-furyl)phosphine (0.12 g, 0.50 mmol) in N,N-dimethylformamide (30 mL) was added. The reaction mixture was warmed to 70° C. and stirred overnight. The mixture was then cooled to room temperature and partitioned between ether and sat. NH4Cl solutions. The organic layers were washed with water, dried over MgSO4, concentrated and purified on silica gel (eluting with 0 to 20% EtOAc in hexanes) to give the desired product (3.87 g, 78%). LCMS calculated for C22H25ClNO4 (M+H)+: m/z=402.1; Found: 402.1,

後処理

  1. temperaturecooled to room temperature
  2. additionwas added
  3. temperatureThe reaction mixture was warmed to 70° C.
  4. stirringstirred overnight
  5. temperatureThe mixture was then cooled to room temperature
  6. custompartitioned between ether and sat. NH4Cl solutions
  7. washThe organic layers were washed with water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. custompurified on silica gel (eluting with 0 to 20% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-78078a31d8f04cde99062af16a4b0615
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

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