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

HRID 1508072Notes

Reaction equation

HRID 1508072 reaction equation
[CH3:1][N:2]([CH3:16])[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:20]1(B(O)O)[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]=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][N:2]([CH3:16])[S:3]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]=2)[CH:9]=1)(=[O:5])=[O:4]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 38629021-Cyclohexenylboronic acidHCID 589943492-(4-Amino-3-bromo-phenyl)-ethanesulfonic acid dimethylamide

Product 1

HCID 589945782-(4-Amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid dimethylamideYield 76.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 477 mg (1.55 mmol) of 2-(4-amino-3-bromo-phenyl)-ethanesulfonic acid dimethylamide (as prepared in the previous step) in toluene (13 mL) and EtOH (6.5 mL) was treated with 215 mg (1.71 mg) of cyclohex-1-enylboronic acid and 6.21 mL (12.4 mmol) of 2.0 M aqueous Na2CO3. The mixture was degassed via sonication, placed under Ar, treated with 179 mg (0.155 mmol) of Pd(PPh3)4, and heated to 80° C. for 17.5 h. The mixture was cooled to RT, diluted with EtOAc (50 mL), and washed with water (2×25 mL). The aqueous layer was extracted with EtOAc (30 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 50% EtOAc-hexane afforded 365 mg (76%) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): δ 6.90 (dd, 1H, J=8.4, 2.4 Hz), 6.84 (d, 1H, J=2.4 Hz), 6.62 (d, 1H, J=8.4 Hz), 5.70-5.66 (m, 1H), 4.03 (br s, 2H), 3.20-3.13 (m, 2H), 2.93-2.87 (m, 2H), 2.83 (s, 6H), 2.24-2.17 (m, 4H), 1.82-1.74 (m, 2H), 1.74-1.66 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C16H24N2O2S, 309.2 (M+H). found 309.1.

Workup

  1. customThe mixture was degassed via sonication
  2. temperatureThe mixture was cooled to RT
  3. washwashed with water (2×25 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (30 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fff2ef161b314ea9b3c8dac4c8dffe75
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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