Potassium Carbonate → 2-(2-Fluoro-6-methoxyphenyl)-1,2-thiazinane 1,1-dioxide

HRID 2055584Notes

Reaction equation

HRID 2055584 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[F:10].[S:11]1(=[O:18])(=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13][NH:12]1.C(=O)([O-])[O-].[K+].[K+]>CO.[Cu]>[F:10][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH3:9])[C:2]=1[N:12]1[CH2:13][CH2:14][CH2:15][CH2:16][S:11]1(=[O:18])=[O:17]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3035081,4-ButanesultamHCID 27793182-Bromo-3-fluoroanisole

Product 1

HCID 692662062-(2-Fluoro-6-methoxyphenyl)-1,2-thiazinane 1,1-dioxide

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 887MethanolSolvent

Procedure

2-Bromo-1-fluoro-3-methoxybenzene (200 mg, 0.975 mmol), 1,2-thiazinane 1,1-dioxide (264 mg, 1.951 mmol), copper (62 mg, 0.975 mmol) and potassium carbonate (270 mg, 1.95 1 mmol) were combined and heated to 170 C for 5 hours. After this time, the mixture was suspended in methanol (15 ml) and vortexed for 18 hours. This mixture was filtered through Gelman Acrodisc and evaporated in vacuo. The resulting residue was partitioned between EtOAc (2×10 ml) and aq NH4Cl (5 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. This residue was purified by column chromatography eluting with a 0-10% EtOAc/CH2Cl2 to give 2-(2-fluoro-6-methoxyphenyl)-1,2-thiazinane 1,1-dioxide. Low resolution mass spectrometry: (M+H+)=260.1. 1H NMR (400 MHz, CDCl3) δ 7.21 (dt, 1H, J=8.1 and 4.3 Hz), 6.69-6.77 (m, 21), 3.88 (s, 3H), 3.75-8.74 (m, 1H), 3.65 (dq, 1H, J=4.6, 6.0 and 14 Hz), 3.24 (dd, 2H, J=5.6 and 7.4 Hz), 3.27 (quin, 2H, J=6.1 Hz) and 1.78-1.90 (m, 2H) ppm.

Workup

  1. temperatureheated to 170 C for 5 hours
  2. filtrationThis mixture was filtered through Gelman Acrodisc
  3. customevaporated in vacuo
  4. customThe resulting residue was partitioned between EtOAc (2×10 ml) and aq NH4Cl (5 ml)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThis residue was purified by column chromatography
  9. washeluting with a 0-10% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-93c57c96160d4b989e601d9dd1fb5deb
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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