4-Methylcyclohexane-1-carbonyl chloride → 5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(ethoxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 1614914Notes

Reaction equation

HRID 1614914 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:19]#[C:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:8][C:9]=1[NH:10][CH2:11][CH2:12][P:13]([O:16][CH2:17][CH3:18])([CH3:15])=[O:14])=[O:4].[CH3:25][CH:26]1[CH2:31][CH2:30][CH:29]([C:32](Cl)=[O:33])[CH2:28][CH2:27]1>N1C=CC=CC=1.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:19]#[C:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:8][C:9]=1[N:10]([CH2:11][CH2:12][P:13]([O:16][CH2:17][CH3:18])([CH3:15])=[O:14])[C:32]([CH:29]1[CH2:30][CH2:31][CH:26]([CH3:25])[CH2:27][CH2:28]1)=[O:33])=[O:4]

Participants

5

Reactant 2

HCID 129863574-Methylcyclohexane-1-carbonyl chlorideHCID 670343375-(3,3-Dimethyl-but-1-ynyl)-3-[2-(ethoxy-methyl-phosphinoyl)-ethylamino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 670337505-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(ethoxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 80.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[2-(ethoxy-methyl-phosphinoyl)-ethylamino]-thiophene-2-carboxylic acid methyl ester (233 mg, 0.629 mmol) was dissolved in pyridine (4 mL) and then 4-methyl-cyclohexanecarbonyl chloride (506 mg, 3.15 mmol) was added. The reaction was stirred for 7 hours at 100° C., the heat to the oil bath was shut off and the reaction was allowed to stir for a further 9 hours. The reaction was diluted with EtOAc and extracted with H2O. The organic phase was then extracted with brine and dried over Na2SO4. The drying agent was removed by vacuum filtration and the filtrate was concentrated. 5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(ethoxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (251 mg, 78%) was isolated from the residue by silica gel column chromatography.

Workup

  1. temperaturethe heat to the oil bath
  2. stirringto stir for a further 9 hours
  3. extractionextracted with H2O
  4. extractionThe organic phase was then extracted with brine
  5. dry with materialdried over Na2SO4
  6. customThe drying agent was removed by vacuum filtration
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-f3453c449dbe4886a96a657d349ed864
Source dataset
uspto-grants-2014_07
Patent number
US08765722B2

Reaction notes

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