Ethyl Acetate → 2-Cyclohex-1-enyl-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamine

HRID 2367794Notes

Reaction equation

HRID 2367794 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH2:16].[C:17]1(B(O)O)[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.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>[C:17]1([C:2]2[CH:7]=[C:6]([CH:8]3[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]3)[CH:5]=[CH:4][C:3]=2[NH2:16])[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 38629021-Cyclohexenylboronic acidHCID 591285552-Bromo-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamine

Product 1

HCID 591285412-Cyclohex-1-enyl-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamineYield 86%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-bromo-4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-phenylamine (as prepared in the previous step, 150 mg, 0.493 mmol), cyclohexen-1-yl boronic acid (70 mg, 0.542 mmol) and Pd(PPh3)4 (57 mg, 0.0493 mmol) in 5 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (2.0 mL, 4.0 mmol). The resulting mixture was stirred at 80° C. for 8 h under Ar, and then cooled to RT. Treated with 50 mL of EtOAc, the mixture was washed with H2O (3×15 mL), brine (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (2-5% EtOAc/DCM) gave 130 mg (86%) of the title compound as a brown solid. 1H-NMR (CDCl3; 400 MHz): δ 6.89 (dd, 1H, J=8.4, 2.3 Hz), 6.84 (d, 1H, J=2.3 Hz), 6.65 (d, 1H, J=8.4 Hz), 5.74 (m, 1H), 3.74 (br s, 2H), 3.08-3.17 (m, 4H), 2.66 (dddd, 1H, J=12.1, 12.1, 3.1, 3.1 Hz), 2.29-2.42 (m, 2H), 2.13-2.25 (m, 6H), 1.73-1.81 (m, 2H), 1.65-1.73 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C17H23NO2S, 306.1 (M+H). found 306.1.

Workup

  1. temperaturecooled to RT
  2. washthe mixture was washed with H2O (3×15 mL), brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-09834d855b204362997d6ea20cd0314b
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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