Cesium carbonate → 5-[4-Difluoromethoxy-3-methoxy-2-(3-methoxymethyl-oxetan-3-ylmethoxy)-phenyl]-2,3-dihydro-isoindol-1-one

HRID 2171108노트

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HRID 2171108 반응식
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2([CH2:14][O:15][CH3:16])[CH2:13][O:12][CH2:11]2)=[C:6]([O:17][CH3:18])[C:5]([O:19][CH:20]([F:22])[F:21])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]3[C:43](=[CH:44][CH:45]=2)[C:42](=[O:46])[NH:41][CH2:40]3)O1>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:21][CH:20]([F:22])[O:19][C:5]1[CH:4]=[CH:3][C:2]([C:37]2[CH:38]=[C:39]3[C:43](=[CH:44][CH:45]=2)[C:42](=[O:46])[NH:41][CH2:40]3)=[C:7]([O:8][CH2:9][C:10]2([CH2:14][O:15][CH3:16])[CH2:13][O:12][CH2:11]2)[C:6]=1[O:17][CH3:18]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 674676123-((6-Bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane

생성물 1

HCID 674627315-[4-Difluoromethoxy-3-methoxy-2-(3-methoxymethyl-oxetan-3-ylmethoxy)-phenyl]-2,3-dihydro-isoindol-1-one수율 22%

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

To a stirring solution of 3-((6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane (200 mg, 0.521 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h. To this cesium carbonate (507 mg, 1.563 mmol), tetrakis(triphenylphosphine) palladium(0) (30 mg, 0.026 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (162 mg, 0.626 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded the title compound as a solid (50 mg, 22%).

후처리

  1. customthe resultant reaction mixture
  2. temperatureThe reaction mixture was cooled to RT
  3. filtrationfiltered
  4. additionthe filtrate was diluted with water
  5. extractionextracted with ethyl acetate (3×)
  6. washThe combined ethyl acetate layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether)

출처 및 근거

ORD 기록
ord-df0dda01eac94e0aa0d6db1f4e8321a2
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051290B2

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