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

HRID 510934노트

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HRID 510934 반응식
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]([CH3:38])=[C:28](I)[C:29]([O:35][CH3:36])=[C:30]([C:32](=[O:34])[CH3:33])[CH:31]=1>CN(C=O)C.[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][CH3:36])=[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]([CH3:38])=[C:26]([Cl:25])[CH:31]=1)(=[O:34])[CH3:33]

참가 물질

9

반응물 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 16244498Benzyl 3-iodoazetidine-1-carboxylateHCID 866667971-(5-Chloro-3-iodo-2-methoxy-4-methylphenyl)ethanone

생성물 1

HCID 86666850Benzyl 3-(3-acetyl-5-chloro-2-methoxy-6-methylphenyl)azetidine-1-carboxylate수율 44%

시약·촉매·용매 4

HCID 23994Zinc촉매HCID 521585Tris(furan-2-yl)phosphane촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매3회

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온도
70 °C

실험 절차

Zinc (1.15 g, 17.6 mmol) was suspended with 1,2-dibromoethane (0.101 mL, 1.17 mmol) in DMF (21 mL). The mixture was heated at 70° C. for 10 min and then cooled to room temperature. Chlorotrimethylsilane (0.149 mL, 1.17 mmol) was added dropwise and stirring was continued for 1 hour. A solution of benzyl 3-iodoazetidine-1-carboxylate (4.6 g, 15 mmol, from Pharmablock) in DMF (20 mL) was then added and the mixture was heated at 40° C. for 1 h before a mixture of 1-(5-chloro-3-iodo-2-methoxy-4-methylphenyl)ethanone (5.0 g, 15 mmol, from Example 60, Step 2), tris(dibenzylideneacetone)dipalladium(0) (0.27 g, 0.29 mmol) and tri-(2-furyl)phosphine (0.14 g, 0.59 mmol) in DMF (40 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 solution. The organic layer was washed with water, dried over MgSO4, concentrated and purified on silica gel (eluting with 0 to 20% EtOAc in hexane) to give the desired product (2.5 g, 44%). LCMS calculated for C21H23ClNO4 (M+H)+: m/z=338.1. found: 388.1.

후처리

  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 solution
  7. washThe organic layer was washed with water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. custompurified on silica gel (eluting with 0 to 20% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-0ba66419aa8243949fcbcd558248f973
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096600B2

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