Sodium Bicarbonate → 3-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73175Notes

Reaction equation

HRID 73175 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:9]=1[NH:10][CH:11]([CH3:13])[CH3:12])=[O:4].[N:20]([CH:23]1[CH2:28][CH:27]([CH3:29])[CH2:26][CH2:25][CH:24]1[C:30](Cl)=[O:31])=[N+:21]=[N-:22].CC1CCC(C(Cl)=O)=CC1.C([O-])(O)=O.[Na+]>ClCCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:8][C:9]=1[N:10]([C:30]([CH:24]1[CH2:25][CH2:26][CH:27]([CH3:29])[CH2:28][CH:23]1[N:20]=[N+:21]=[N-:22])=[O:31])[CH:11]([CH3:13])[CH3:12])=[O:4]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 11737447Methyl 3-(isopropyl-amino)-5-phenylthiophene-2-carboxylateHCID 187949664-Methylcyclohex-1-ene-1-carbonyl chlorideHCID 597523922-Azido-4-methyl-cyclohexanecarboxylic acid chloride

Product 1

HCID 597523943-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 49%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-Isopropylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester (227 mg, 0.824 mmol) in 1,2-dichloroethane (2.5 ml) was added the 2:1 mixture of 2-Azido-4-methyl-cyclohexanecarboxylic acid chloride and 4-Methyl-cyclohex-1-enecarboxylic acid chloride (182 mg, 0.906 mmol) dissolved in 1,2-dichloroethane (0.5 ml). The resulting solution was stirred for 18 h at 90° C. and then cooled to room temperature. It was then diluted with ethyl acetate (10 ml) and a solution of saturated NaHCO3 (10 ml). The aqueous phase was separated and washed with ethyl acetate (2×10 ml) and the combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0% to 20% EtOAc/Hexane) to obtain 178 mg (49%) of 3-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester.

Workup

  1. temperaturecooled to room temperature
  2. customThe aqueous phase was separated
  3. washwashed with ethyl acetate (2×10 ml)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (0% to 20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-a2cf9bd1990742a683df51282057860a
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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