Dimethylformamide → 5-fluoro-1-oxo-2,3-dihydro-1H-indene-4-carbonitrile

HRID 1187035노트

반응식

HRID 1187035 반응식
Br[C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:12].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[CH3:42][N:43](C=O)C>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].[C-]#N.[Zn+2].[C-]#N.O>[F:11][C:10]1[CH:9]=[CH:8][C:7]2[C:6](=[O:12])[CH2:5][CH2:4][C:3]=2[C:2]=1[C:42]#[N:43]

참가 물질

7

반응물 3

HCID 6228DimethylformamideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 666462974-bromo-5-fluoro-2,3-dihydro-1H-inden-1-one

생성물 1

HCID 552745775-fluoro-1-oxo-2,3-dihydro-1H-indene-4-carbonitrile

시약·촉매·용매 3

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

반응 조건

온도
175 °C

실험 절차

To a microwave tube charged with 4-bromo-5-fluoro-2,3-dihydro-1H-inden-1-one (500 mg, 2.2 mmol) and a stir bar was added Pd2(dba)3 (40.0 mg, 0.044 mmol), S-phos (45 mg, 0.11 mmol), zinc cyanide (333 mg, 2.84 mmol), DMF (15 mL), and Water (0.15 mL). The tube was sealed, and purged three times with nitrogen. The reaction was then heated to 175° C. for 3 minutes in a microwave reactor. TLC showed formation of the desired product, along with a small amount of the dimethylaniline adduct. The crude product mixture was diluted with EtOAc, washed with brine, dried over sodium sulfate, adsorbed onto silica, and purified by MPLC. After removal of solvent, 5-fluoro-1-oxo-2,3-dihydro-1H-indene-4-carbonitrile was collected.

후처리

  1. customThe tube was sealed
  2. custompurged three times with nitrogen
  3. additionThe crude product mixture was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. custompurified by MPLC
  7. customAfter removal of solvent, 5-fluoro-1-oxo-2,3-dihydro-1H-indene-4-carbonitrile
  8. customwas collected

출처 및 근거

ORD 기록
ord-304d0ade45304a72828aab32bd3ad821
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673920B2

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