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

HRID 1187035Notes

Reaction equation

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]

Participants

Conditions

Temperature: 175 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-304d0ade45304a72828aab32bd3ad821
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673920B2

Reaction notes

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