p-Toluenesulfonic acid → 4-Diethoxymethyl-10-methyl-phenothiazine

HRID 2395113Notes

Reaction equation

HRID 2395113 reaction equation
[CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.[CH3:11][N:12]1[C:25]2[CH:24]=[CH:23][CH:22]=[C:21](C=O)[C:20]=2[S:19][C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>CO.C(OCC)C>[CH2:9]([O:8][CH:1]([O:5][CH2:6][CH3:7])[C:21]1[C:20]2[S:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH3:11])[C:25]=2[CH:24]=[CH:23][CH:22]=1)[CH3:10]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 516892Sodium BicarbonateHCID 381215410-Methylphenothiazine-4-carbaldehyde

Product 1

HCID 189725154-Diethoxymethyl-10-methyl-phenothiazineYield 96.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

15.0 ml of triethyl orthoformate were added at room temperature to a solution of 4.90 g (20.3 mmol) of 10-methylphenothiazine-4-carbaldehyde and 50 mg of p-toluenesulphonic acid×1H2O in 15 ml of methanol. The reaction mixture was boiled at reflux for 45 minutes, cooled and poured into 30 g of ice, 30 ml of saturated aqueous sodium hydrogen carbonate solution and 100 ml of diethyl ether. The organic phase was washed with 50 ml of saturated sodium chloride solution, dried over magnesium sulphate and concentrated. The residue was chromatographed on 300 g of silica gel with diethyl ether/hexane (1:4), whereupon, after crystallization from diethyl ether/hexane in a refrigerator, 6.16 g (96.2%) of 4-diethoxymethyl-10-methyl-phenothiazine were obtained as a white solid of m.p. 44.6°-46.2°.

Workup

  1. temperatureat reflux for 45 minutes
  2. temperaturecooled
  3. washThe organic phase was washed with 50 ml of saturated sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. customThe residue was chromatographed on 300 g of silica gel with diethyl ether/hexane (1:4), whereupon
  7. customafter crystallization from diethyl ether/hexane in a refrigerator

Sources & evidence

ORD record
ord-05396b1ff312470c9f913179f18ac425
Source dataset
uspto-grants-1998_09
Patent number
US05811389

Reaction notes

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