1-Piperidinecarboxaldehyde → [6-(Tert.-butyl-dimethyl-silanyloxymethyl)-3,7-dimethoxy-10-methyl-phenothiazine4-yl]methanol

HRID 2395129Notes

Reaction equation

HRID 2395129 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:28])([CH3:27])[C:8]1[C:21]2[S:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=3)[N:13]([CH3:24])[C:12]=2[CH:11]=[CH:10][C:9]=1[O:25][CH3:26])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH:34](N1CCCCC1)=[O:35].COC1C=C(C=O)C2N(C)C3C(SC=2C=1C(C(C)(C)C)O[SiH](C)C)=CC(OC)=CC=3.[BH4-].[Li+]>C(OCC)C.O1CCCC1.O1CCCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:28])([CH3:27])[C:8]1[C:9]([O:25][CH3:26])=[CH:10][CH:11]=[C:12]2[C:21]=1[S:20][C:19]1[C:18]([CH2:34][OH:35])=[C:17]([O:22][CH3:23])[CH:16]=[CH:15][C:14]=1[N:13]2[CH3:24])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 174291-PiperidinecarboxaldehydeHCID 4148881Lithium borohydrideHCID 131720844Tert-butyl-[2-(3,7-dimethoxy-10-methylphenothiazin-4-yl)propan-2-yloxy]silaneHCID 178418339ButyllithiumHCID 178487337HCID 178487337, compound

Product 1

HCID 137329065[6-(Tert.-butyl-dimethyl-silanyloxymethyl)-3,7-dimethoxy-10-methyl-phenothiazine4-yl]methanolYield 67.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21868444Ether tetrahydrofuranSolvent

Procedure

A solution of 4.56 g (10.9 mmol) of 4-(tert.-butyl-dimethyl-silanyloxymethyl)-3,7-dimethoxy-10-methyl-phenothiazine in 50 ml of diethyl ether/tetrahydrofuran (4:1) was reacted with 7.5 ml of n-butyllithium solution (1.6M in hexane) and 1.89 g (16.84 mmol) of N-formylpiperidine analogously to that described in Example 4.1.1c. The resulting 3,7-dimethoxy-4-(tert.butyldimethylsilanyloxymethyl)-10-methylphenothiazine-carbaldehyde was dissolved in 50 ml of tetrahydrofuran and reduced with 12.0 ml of lithium borohydride solution (1M in tetrahydrofuran) analogously to that described in Example 4.1.8.b. The reaction mixture was poured into ice/1M sodium dihydrogen phosphate solution, whereupon the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel with ethyl acetate/hexane (1:1), whereupon, after recrystallization from ethyl acetate/hexane and drying, 3.30 g (67.6%) of [6-(tert.-butyl-dimethyl-silanyloxymethyl)-3,7-dimethoxy-10-methyl-phenothiazine4-yl]methanol were obtained as a white solid of m.p. 46°-47°.

Workup

  1. extractionwas extracted three times with ethyl acetate
  2. washThe combined organic phases were washed with saturated sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel with ethyl acetate/hexane (1:1), whereupon
  6. customafter recrystallization from ethyl acetate/hexane
  7. customdrying

Sources & evidence

ORD record
ord-8de15f299b13423ba3d7941c50ba23ab
Source dataset
uspto-grants-1998_09
Patent number
US05811389

Reaction notes

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