Potassium Carbonate → Methyl 3-tert-butoxy-2-{[(4-ethoxyphenyl)sulfonyl]-4-methylanilino}propanoate

HRID 971323Notes

Reaction equation

HRID 971323 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)[CH3:2].Br[CH:22]([CH2:27][O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([O:25][CH3:26])=[O:24].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:29]([O:28][CH2:27][CH:22]([N:13]([S:10]([C:7]1[CH:6]=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[CH:9][CH:8]=1)(=[O:11])=[O:12])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)[C:23]([O:25][CH3:26])=[O:24])([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 9250104-ethoxy-N-(4-methylphenyl)benzenesulfonamideHCID 76681185Methyl 2-bromo-3-(tert-butoxy)propanoate

Product 1

HCID 11662368Methyl 3-tert-butoxy-2-{[(4-ethoxyphenyl)sulfonyl]-4-methylanilino}propanoateYield 26.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

The crude N-aryl-benzenesulfonamide building block XIII, e.g. 4-ethoxy-N-(4-methylphenyl)benzenesulfonamide (388 mg, 1.33 mmol, preparation described in example 1, step a)), was dissolved in DMF (5 mL). Intermediate XI with R3═CH2OtBu, e.g. methyl 2-bromo-3-tert-butoxypropanoate (478 mg, 2 mmol) and potassium carbonate (368 mg, 2.66 mmol) were added. The mixture was heated overnight at 60° C. Solvents were evaporated. The crude residue was suspended in ethyl acetate (10 mL) and was washed with 1N HCl solution (7 mL) and with brine (7 mL). Organic phase was dried over MgSO4, fitrated and evaporated. The crude mixture was purified by flash chromatography, using a 8:2 mixture cyclohexane/ethyl acetate as eluent. The desired product, e.g. methyl 3-tert-butoxy-2-{[(4-ethoxyphenyl)sulfonyl]-4-methylanilino}propanoate (157 mg, 26.3%) was isolated as a light yellow oil, in 96.4% purity by HPLC (MaxPlot detection between 230 and 400 nm).

Workup

  1. customSolvents were evaporated
  2. washwas washed with 1N HCl solution (7 mL) and with brine (7 mL)
  3. dry with materialOrganic phase was dried over MgSO4
  4. customevaporated
  5. customThe crude mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-7b7114bc936843a69d8f2076d030dcf6
Source dataset
uspto-grants-2007_12
Patent number
US07312358B2

Reaction notes

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