4-Methylcyclohex-3-ene-1-carbonyl chloride → 5-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 73166Notes

Reaction equation

HRID 73166 reaction equation
[CH3:1][C:2]1[CH2:7][CH2:6][CH:5]([C:8]([Cl:10])=[O:9])[CH2:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:18][C:19]=1[NH:20][CH:21]([CH3:23])[CH3:22])=[O:14]>ClCCCl>[CH3:1][C:2]1[CH2:7][CH2:6][CH:5]([C:8]([Cl:10])=[O:9])[CH2:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)=[CH:18][C:19]=1[N:20]([CH:21]([CH3:23])[CH3:22])[C:8]([CH:5]1[CH2:6][CH2:7][C:2]([CH3:1])=[CH:3][CH2:4]1)=[O:9])=[O:14]

Participants

5

Reactant 2

HCID 129514754-Methylcyclohex-3-ene-1-carbonyl chlorideHCID 597523015-(4-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl ester

Product 2

HCID 129514754-Methylcyclohex-3-ene-1-carbonyl chlorideHCID 597522855-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 87.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4-Methyl-cyclohex-3-enecarbonyl chloride was prepared according to the procedure reported in Journal of Organic Chemistry (1986) 51(23), PP4485-8. This 4-Methyl-cyclohex-3-enecarbonyl chloride (0.121 g, 0.77 mmol) was dissolved along with 5-(4-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl ester (0.150 g, 0.51 mmol) in anhydrous 1,2-dichloroethane (2 mL). The reaction mixture was stirred for 16 h at reflux. Then, the solvents were removed and the residue was purified by flash chromatography (8:2 Hexane/EtOAc) to obtain 140 mg (66%) of 5-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester. 1H NMR (CDCl3, 400 MHz): δ 7.60 (m, 2H), 7.15 (m, 2H), 7.02 (d, 1H), 5.42-5.20 (m, 1H), 4.99 (m, 1H), 3.83 (d, 3H), 2.41-1.50 (m, 10H), 1.20 (m, 3H), 0.98 (d, 3H).

Workup

  1. temperatureat reflux
  2. customThen, the solvents were removed
  3. customthe residue was purified by flash chromatography (8:2 Hexane/EtOAc)

Sources & evidence

ORD record
ord-b672648e8be94a34932992ea1e0c8898
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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