Methanol → 1-Methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin-4(3H)-one 2,2-Dioxide

HRID 411232Notes

Reaction equation

HRID 411232 reaction equation
[CH3:1][N:2]([S:23]([CH3:26])(=[O:25])=[O:24])[C:3]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][CH2:15][O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)=[CH:9][C:4]=1[C:5]([O:7]C)=O.[H-].[Na+].CO>CN(C=O)C>[CH3:1][N:2]1[C:3]2[CH:12]=[CH:11][C:10]([C:13]#[C:14][CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:9][C:4]=2[C:5](=[O:7])[CH2:26][S:23]1(=[O:25])=[O:24]

Participants

5

Reactant 3

HCID 887MethanolHCID 24758Sodium hydrideHCID 22397172methyl 2-(methyl(methylsulfonyl)amino)-5-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)benzoate

Product 1

HCID 223971711-Methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin-4(3H)-one 2,2-DioxideYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 2-(methyl(methylsulfonyl)amino)-5-(3-(tetrahydro-2H-pyran -2-yloxy)-1-propynyl)benzoate (Preparation 51, 0.93 g) in DMF (15 mL) at 0° C. is added NaH (0.20 g; 60% dispersion in mineral oil) portionwise. The reaction mixture is warmed to ambient temperature stirring for 1 h upon which methanol (4 mL) is added and the organic portion is washed with a saturated solution of citric acid (50 mL). The aqueous layer is extracted with Et2O (2×50 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude orange liquid is purified by silica gel column chromatography (2/1, hexanes/EtOAc) to afford 0.59g (69%) of the title compound as a white solid. Physical characteristics: m.p. 107-108° C.; 1H NMR (300 MHz, CDCl3) δ 8.21, 7.71, 7.10, 4.87, 4.48, 4.33, 3.88, 3.55, 3.44, 1.79, 1.62; IR (diffuse reflectance) 2962, 2908, 1684, 1493, 1339, 1211, 1204, 1156, 1135, 1130, 1123, 1030, 899, 886, 838 cm−1; MS (ESI−) 348 (M−H−). Anal. Found: C, 58.37; H, 5.58; N, 3.96.

Workup

  1. additionis added
  2. washthe organic portion is washed with a saturated solution of citric acid (50 mL)
  3. extractionThe aqueous layer is extracted with Et2O (2×50 mL)
  4. customThe organic layer is separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude orange liquid is purified by silica gel column chromatography (2/1, hexanes/EtOAc)

Sources & evidence

ORD record
ord-6317960775c14862b5e209821ae61361
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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