Methyl Thioglycolate → Methyl 4-bromo-7-fluorobenzo[b]thiophene-2-carboxylate
Reaction equation
[Br:1][C:2]1[C:7]([CH:8]=O)=[C:6](F)[C:5]([F:11])=[CH:4][CH:3]=1.[C:12]([O:16][CH3:17])(=[O:15])[CH2:13][SH:14]>>[Br:1][C:2]1[C:7]2[CH:8]=[C:13]([C:12]([O:16][CH3:17])=[O:15])[S:14][C:6]=2[C:5]([F:11])=[CH:4][CH:3]=1Participants
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-1403539c5e6a46c88f85c2ff7c5059ea
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06900216B2
Reaction notes
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