Methyl iodide → 3-[(4-Methoxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid

HRID 73186Notes

Reaction equation

HRID 73186 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[H-].[Na+].I[CH3:36]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:36][O:26][CH:23]1[CH2:24][CH2:25][CH:20]([N:10]([C:11]([CH:13]2[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]2)=[O:12])[C:9]2[CH:8]=[C:7]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[S:6][C:5]=2[C:3]([OH:2])=[O:4])[CH2:21][CH2:22]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 597523083-[(4-Hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 100270503-[(4-Methoxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acidYield 18.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-[(4-Hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (27 mg, 0.059 mmol) was dissolved in THF (0.6 ml), cooled to 0° C. in an ice bath and 60% sodium hydride (5 mg, 0.118 mmol) was added, followed by a catalytic amount of tetrabutylammonium iodide. After stirring for 1 hour, iodomethane (37 ul, 0.590 mmol) was added and the reaction further stirred for 3 hours. It was then quenched with water (5 ml) and extracted with ethyl acetate (3×5 ml). The combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by preparative chromatography (10% MeOH/CH2Cl2) to obtain 5 mg (18%) of 3-[(4-Methoxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (compound 46).

Workup

  1. customthe reaction
  2. stirringfurther stirred for 3 hours
  3. customIt was then quenched with water (5 ml)
  4. extractionextracted with ethyl acetate (3×5 ml)
  5. dry with materialThe combined ethyl acetate layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by preparative chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-52e359780f774015a773d2b0557c3416
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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