Hydrochloric Acid → 6-Diethoxymethyl-10-methylphenothiazine-4-carbaldehyde

HRID 2395162Notes

Reaction equation

HRID 2395162 reaction equation
C([Li])(C)(C)C.[CH2:6]([O:8][CH:9]([O:25][CH2:26][CH3:27])[C:10]1[C:23]2[S:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH3:24])[C:14]=2[CH:13]=[CH:12][CH:11]=1)[CH3:7].CN(C)CCN(C)C.[CH:36](N1CCCCC1)=[O:37].Cl>C(OCC)C.C(OCC)(=O)C>[CH2:6]([O:8][CH:9]([O:25][CH2:26][CH3:27])[C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:23]=1[S:22][C:21]1[C:20]([CH:36]=[O:37])=[CH:19][CH:18]=[CH:17][C:16]=1[N:15]2[CH3:24])[CH3:7]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 174291-PiperidinecarboxaldehydeHCID 189725154-Diethoxymethyl-10-methyl-phenothiazineHCID 178418306HCID 178418306, compound

Product 1

HCID 189724746-Diethoxymethyl-10-methylphenothiazine-4-carbaldehydeYield 19.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

7.4 ml of tert-butyllithium solution (1.4M in pentane) were slowly added dropwise under argon and at -78° to a solution of 2.5 g (7.93 mmol) of 4-diethoxymethyl-10-methyl-phenothiazine and 2.4 ml of N,N,N',N'-tetramethylethylenediamine in 25 ml of diethyl ether. The reaction mixture was brought slowly to room temperature, stirred for 3.5 hours and then treated with 1.32 ml (11.9 mmol) of N-formylpiperidine. The reaction mixture was stirred at 0° for 1 hour and then poured into 30 g of ice, 30 ml of 0.1N aqueous hydrochloric acid solution and 70 ml of ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulphate and evaporated. The residue was chromatographed on 200 g of silica gel with ethyl acetate/hexane (1:4), whereupon 310 mg (12.4%) of starting product and, after crystallization from ethyl acetate/hexane, 520 mg (19%) of 6-diethoxymethyl-10-methyl-phenothiazine-4-carbaldehyde were obtained as a yellow solid of m.p. 154°-154.5°.

Workup

  1. customwas brought slowly to room temperature
  2. stirringThe reaction mixture was stirred at 0° for 1 hour
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialthe combined organic phases were dried over magnesium sulphate
  5. customevaporated
  6. customThe residue was chromatographed on 200 g of silica gel with ethyl acetate/hexane (1:4), whereupon 310 mg (12.4%) of starting product
  7. customafter crystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-a47873f9c62243c6964102d3545f7d88
Source dataset
uspto-grants-1998_09
Patent number
US05811548

Reaction notes

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