N-methyl-2-pyrrolidone → Methyl 3-amino-6-(trifluoromethyl)benzo[b]thiophene-2-carboxylate

HRID 1986924Notes

Reaction equation

[N+]([C:4]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7])([O-])=O.[C:16]([O:20][CH3:21])(=[O:19])[CH2:17][SH:18].CN1C(=O)CCC1.O.[OH-].[Li+]>O>[C:16]([C:17]1[S:18][C:4]2[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:5]=2[C:6]=1[NH2:7])([O:20][CH3:21])=[O:19]

Participants

Conditions

Temperature: 2 °C

Procedure

A 22-L, 3-necked, round-bottom flask equipped with a mechanical stirrer, nitrogen bubbler, and a thermocouple probe, was charged with 1.20 kg (5.55 mole) of 2-nitro-4-trifluoromethylbenzonitrile, 589.3 g (496 mL, 5.55 mole) of methyl thioglycolate, and 4.3 L of NMP. After the resulting yellow solution was cooled to 2° C., a solution prepared from 466.0 g (11.11 mole, 2.0 eq) of lithium hydroxide monohydrate in 3.36 L of water was slowly added over a period of 78 min while maintaining a temperature of 2-20° C. The brown slurry was allowed to warm to 21° C. over a 2 h period, then was diluted with 8.0 L of water (Texo->27° C.). After stirring for 40 min and cooling to 18° C., product was collected by filtration, rinsing with 10 L of water, then air-drying at ambient temperature to give 1.295 kg (84.7% yield) of 2-carbomethoxy-3-amino-6-trifluoromethylbenzo[b]thiophene, as a light-yellow solid.

Workup

additionwas slowly added over a period of 78 min
temperaturewhile maintaining a temperature of 2-20° C
temperatureto warm to 21° C. over a 2 h period
temperaturecooling to 18° C.
filtrationproduct was collected by filtration
washrinsing with 10 L of water
customair-drying at ambient temperature

Sources & evidence

ORD record: ord-24b14f7863dc4971af8c10ef719d95ca
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550469B2

Reaction notes

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