Triphenylphosphine → 3-[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-2-carboxylic acid methyl ester

HRID 749335Notes

Reaction equation

HRID 749335 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[CH:8][C:9]=1[NH:10][CH:11]([CH3:13])[CH3:12])=[O:4].Cl[C:22]([CH:24]1[CH2:29][CH2:28][CH:27]([CH3:30])[CH2:26][CH:25]1[O:31][C:32](=[O:34])[CH3:33])=[O:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCCl.C(Cl)(Cl)Cl.O>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[CH:8][C:9]=1[N:10]([C:22]([CH:24]1[CH2:29][CH2:28][CH:27]([CH3:30])[CH2:26][CH:25]1[O:31][C:32](=[O:34])[CH3:33])=[O:23])[CH:11]([CH3:13])[CH3:12])=[O:4]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 597523715-(3-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl esterHCID 597523912-Acetoxy-4-methyl-cyclohexanecarboxylic acid chloride

Product 1

HCID 597523393-[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-2-carboxylic acid methyl esterYield 12.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 5-(3-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl ester (200 mg, 0.683 mmol) in 1,2-dichloroethane (5 mL), acetic acid 2-chlorocarbonyl-5-methyl-cyclohexyl ester (148 mg, 0.679 mmol) and triphenylphosphine (197 mg, 0.751 mmol) were added under an atmosphere of N2. The reaction mixture was refluxed for 12 h and then diluted with chloroform and water. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified by preparative TLC plate using 15% ethyl acetate in hexane to obtain 3[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-2-carboxylic acid methyl ester as a white solid (40 mg, 12%). 1H NMR (CDCl3, 400 MHz): δ7.45-7.25 (m, 4H), 7.13-6.95 (m, 1H), 5.13 (m, 1H) 4.87-4.75 (m, 1H), 3.80 (s, 3H), 2.37-0.62 (m, 20H).

Workup

  1. temperatureThe reaction mixture was refluxed for 12 h
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative TLC plate

Sources & evidence

ORD record
ord-755c29edb07c4efc8a54e218674d3f7c
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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