4-Bromo-1,2-difluorobenzene → 6-Bromo-2,3-difluorobenzaldehyde

HRID 2183683Notes

Reaction equation

HRID 2183683 reaction equation
FC1C2SC=CC=2C([C:11](=[O:14])CC)=CC=1.[Br:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=1>CN(C)C=O>[Br:15][C:16]1[C:17]([CH:11]=[O:14])=[C:18]([F:23])[C:19]([F:22])=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 676754-Bromo-1,2-difluorobenzeneHCID 224741461-(7-Fluorobenzo[b]thiophen-4-yl)propan-1-one

Product 1

HCID 98778516-Bromo-2,3-difluorobenzaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a similar manner to Example 9 Method A, 1-(7-fluorobenzo[b]thiophen-4-yl)propan-1-one was prepared starting from 4-bromo-1,2-difluorobenzene (39.7 g). This was lithiated and reacted with dimethylformamide to give 6-bromo-2,3-difluorobenzaldehyde (41.3 g) as a yellow solid. The aldehyde was reacted with methyl thioglycolate (14.6 ml) to give methyl 4-bromo-7-fluorobenzo[b]thiophene-2-carboxylate (31.2 g) as a yellow solid. The ester was hydrolysed to give 4-bromo-7-fluorobenzo[b]thiophene-2-carboxylic acid (37.25 g) as a yellow solid which was decarboxylated using copper and quinoline at 170-180° C. for 4 hours to give 4-bromo-7-fluorobenzo[b]thiophene (18.2 g) as a white solid, m.p. 47-48° C. This compound (7.4 g) was reacted with magnesium (0.85 g) and then with N-methoxy-N-methylpropionamide (5.6 g) to give 1-(7-fluorobenzo[b]thiophen-4-yl)propan-1-one (2.1 g) as an oil which was used without further purification.

Sources & evidence

ORD record
ord-b69f8664c2eb43cc925b098fcb5c26a3
Source dataset
uspto-grants-2005_05
Patent number
US06900216B2

Reaction notes

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