Ethanol → 2-(4-Amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid methylamide

HRID 1190145Notes

Reaction equation

HRID 1190145 reaction equation
[CH3:1][NH:2][S:3]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10](Br)[CH:9]=1)(=[O:5])=[O:4].CCO.[C:19]1(B(O)O)[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][NH:2][S:3]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=2)[CH:9]=1)(=[O:5])=[O:4]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 38629021-Cyclohexenylboronic acidHCID 589944252-(4-Amino-3-bromo-phenyl)-ethanesulfonic acid methylamide

Product 1

HCID 589945302-(4-Amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid methylamideYield 69.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 177 mg (0.604 mmol) of 2-(4-amino-3-bromo-phenyl)-ethanesulfonic acid methylamide (as prepared in the previous step) in toluene (5 mL) and EtOH (2.5 mL) was treated with 83.7 mg (0.664 mmol) of cyclohex-1-enylboronic acid and 2.40 mL (4.83 mmol) of 2.0 M aqueous Na2CO3. The mixture was degassed via sonication, placed under Ar, treated with 67.3 mg (0.0604 mmol) of Pd(PPh3)4, and heated to 80° C. for 19 h. The mixture was diluted with EtOAc (15 mL) and washed with water (1×10 mL). The aqueous layer was extracted with EtOAc (1×10 mL), and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 25-g Varian MegaBond Elut SPE column with 50% EtOAc-hexane afforded 123 mg (69%) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): δ 6.90 (dd, 1H, J=8.0, 2.0 Hz), 6.83 (d, 1H, J=2.0 Hz), 6.32 (d, 1H, J=8.0 Hz), 5.70-5.66 (m, 1H), 4.97-4.90 (m, 2H), 4.08-3.99 (br s, 2H), 3.24-3.17 (m, 2H), 2.91-2.84 (m, 2H), 2.66 (d, 3H, J=5.2 Hz), 2.24-2.15 (m, 4H), 1.82-1.74 (m, 2H), 1.74-1.66 (m, 2H).

Workup

  1. customThe mixture was degassed via sonication
  2. washwashed with water (1×10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (1×10 mL)
  4. dry with materialthe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f36cf64bf7e4b7bb602797bf4d97687
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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