Sodium Carbonate → HCID 23568414, compound

HRID 1822712Notes

Reaction equation

HRID 1822712 reaction equation
[C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]([CH3:15])[S:11]([CH3:14])(=[O:13])=[O:12])#[N:2].Cl.[CH3:17][NH:18][OH:19].C(=O)([O-])[O-].[Na+].[Na+].[C:26]([C:33]([O:35][CH2:36][CH3:37])=[O:34])#[C:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>C(OCC)(=O)C.O.C(O)C>[CH2:36]([O:35][C:33]([C:26]1([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[O:19][N:18]([CH3:17])[C:1]([C:3]2[C:4]([N:10]([S:11]([CH3:14])(=[O:13])=[O:12])[CH3:15])=[CH:5][CH:6]=[CH:7][C:8]=2[F:9])=[N:2]1)=[O:34])[CH3:37]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 69803Diethyl acetylenedicarboxylateHCID 77906N-methylhydroxylamine hydrochlorideHCID 22169652HCID 22169652, compound

Product 1

HCID 23568414HCID 23568414, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of N-(2-cyano-3-fluoro-phenyl)-N-methyl-methanesulfonamide (0.685 g, 3.0 mmol) and N-methylhydroxylamine hydrochloride (1.0 g, 12 mmol) in 1:1 water/ethanol (20 mL) was added sodium carbonate (0.936 g, 6 mmol) in small portions and the resulting mixture stirred at 80° C. for 4 h. The reaction mixture was concentrated and the residue re-dissolved into 1:1 water :ethanol (20 mL). To this solution was added diethyl acetylenedicarboxylate (0.64 mL, 4 mmol) and the mixture stirred for 1 h at room temperature. The reaction mixture was then taken up in ethyl acetate (100 mL), washed successively with water and brine (50 mL each), dried (MgSO4), filtered and concentrated to give a yellow oil. The crude product was purified on silica gel column (2:3 to 3:2 ethyl acetate/hexanes) to afford the title compound as a viscous yellow oil (0.7453 g, 56% yield). 1HNMR (500 MHz, CDCl3) δ: 7.52–7.48 (1H, m), 7.31 (1H, d, J=8.24 Hz), 7.18 (1H, t, J=8.55 Hz), 4.35–4.25 (2H, m), 4.18 (2H, q, J=7.02 Hz), 3.40 (1H, d, J=16.48 Hz), 3.21 (3H, s), 3.09 (1H, d, J=16.48 Hz), 3.09 (3H, s), 3.07 (3H, s), 1.33 (3H, t, J=7.02 Hz), 1.26 (3H, t, J=7.02 Hz). HRMS (ESI) calcd for C18H25FN3O7S (M+H): 446.1397; found: 446.1383.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue re-dissolved into 1:1 water
  3. stirringthe mixture stirred for 1 h at room temperature
  4. washwashed successively with water and brine (50 mL each)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil
  9. customThe crude product was purified on silica gel column (2:3 to 3:2 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1adb7810423a49a491e3de72c624a1d8
Source dataset
uspto-grants-2006_05
Patent number
US07037908B2

Reaction notes

Loading…