3-[Isopropyl-(4-oxo-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester → 3-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 1807966Notes

Reaction equation

HRID 1807966 reaction equation
[CH2:1]([Li])CCC.[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:13][C:14]=1[N:15]([CH:25]([CH3:27])[CH3:26])[C:16]([CH:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)=[O:17])=[O:9]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:13][C:14]=1[N:15]([CH:25]([CH3:26])[CH3:27])[C:16]([CH:18]1[CH2:23][CH2:22][C:21](=[CH2:1])[CH2:20][CH2:19]1)=[O:17])=[O:9]

Participants

5

Reactant 2

HCID 597523673-[Isopropyl-(4-oxo-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterHCID 178418339Butyllithium

Product 1

HCID 597522963-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Butyllithium (2.5 M, 0.9 mL, 2.280 mmol) was added to a cold solution (−78° C.) of methyltriphenylphosphonium bromide (939 mg, 2.630 mmol) in THF (10 mL). The reaction mixture was stirred at room temperature for 1 h and then 3-[Isopropyl-(4-oxo-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester. (700 mg, 1.754) in THF (5 mL) was added at −78° C. The reaction mixture was allowed to stir at room temperature for 12 h. The reaction was quenched by adding saturated solution of NH4Cl and diluted with ethyl acetate. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using ethyl acetate:hexane (1:4) to obtain 3-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (300 mg, 43%) as a solid. 1H NMR (CDCl3, 400 MHz): δ7.63 (d, 2H), 7.50-7.38 (m, 3H), 7.12 (s, 1H), 4.99 (m, 1H), 4.55 (d, 2H), 3.85 (s, 3H), 2.25 (m, 3H), 1.83-1.63 (m, 5H), 1.50 (m, 1H), 1.25 (d, 3H), 0.99 (d, 3H).

Workup

  1. stirringto stir at room temperature for 12 h
  2. customThe reaction was quenched
  3. additionby adding saturated solution of NH4Cl
  4. additiondiluted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-84b44edabf8e4c53ae1a4a1b2ffab07f
Source dataset
uspto-grants-2013_01
Patent number
US08357718B2

Reaction notes

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