Phosphorus oxychloride → Ethyl (7-methoxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)acetate

HRID 30985Notes

Reaction equation

HRID 30985 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[S:17](=[O:20])(=[O:19])[NH2:18])=O)[CH3:2].P(Cl)(Cl)(Cl)=O>>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1[NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[S:17](=[O:20])(=[O:19])[N:18]=1)[CH3:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 69309267N-(4-Methoxy-2-sulfamoyl-phenyl)-malonamic acid ethyl ester

Product 1

HCID 46941516Ethyl (7-methoxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)acetateYield 79%

Procedure

A mixture of 10 (8.0 g, 28 mmol) in phosphorous oxychloride (150 mL, 1.64 mol) was heated to reflux for 2.5 hours, then cooled to room temperature and concentrated in vacuo. The residue was then dissolved in ethyl acetate and neutralized with saturated aqueous sodium bicarbonate. The organic phase was washed with 2 N hydrochloric acid and then brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The solid product was then triturated in diethyl ether to produce 6.6 g of the desired product (4a) as a brown solid in 79% yield. See procedure described in International Patent Application No. PCT/US03/16374. 1H NMR (400 MHz, DMSO-d6): δ12.20 (s, 1H), 7.27 (m, 2 H), 7.20 (s, 1H), 4.14 (q, 2H, J=7.2 Hz), 3.73 (s, 3H), 3.66 (s, 2H), 1.21 (t, 3H, J=7.6 Hz); LC-MS (ESI+): m/e=299.1 [M+1]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2.5 hours
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was then dissolved in ethyl acetate and neutralized with saturated aqueous sodium bicarbonate
  5. washThe organic phase was washed with 2 N hydrochloric acid
  6. dry with materialbrine, dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe solid product was then triturated in diethyl ether

Sources & evidence

ORD record
ord-c22644c799334538a84b730db18ddb84
Source dataset
uspto-grants-2008_09
Patent number
US07425552B2

Reaction notes

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