Hydrochloric Acid → HCID 18972482, compound

HRID 2395120Notes

Reaction equation

HRID 2395120 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:14]=3[O:13][C:12]=2[C:24]=1[CH2:25][O:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH3:32].[CH:33](N1CCCCC1)=[O:34].Cl>O1CCCC1.C(OCC)C>[CH3:23][O:22][C:20]1[CH:19]=[CH:18][C:15]2[N:16]([CH3:17])[C:11]3[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[C:24]([CH2:25][O:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH3:32])[C:12]=3[O:13][C:14]=2[C:21]=1[CH2:33][OH:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 174291-PiperidinecarboxaldehydeHCID 18972543HCID 18972543, compoundHCID 178418339Butyllithium

Product 1

HCID 18972482HCID 18972482, compoundYield 88.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

8.9 ml of n-butyllithium solution were added under argon at -78° to a solution of 4.10 g (10.92 mmol) of 3,7-dimethoxy-4-[[(2-methoxyethoxy)methoxy]methyl]-10-methyl-10H-dibenzo-[b,e][1,4]oxazine in 10 ml of tetrahydrofuran and 40 ml of diethyl ether. The reaction mixture was brought slowly to 0° and stirred for 1.5 hours, whereupon the suspension was treated with 1.82 ml (1.5 eq.) of N-formylpiperidine, stirred at 0° for 30 minutes and poured into 100 g of ice, 100 ml of 0.1N hydrochloric acid solution and 150 ml of diethyl ether. The aqueous phase was extracted three times with chloroform and the combined organic phases were dried over MgSO4 and evaporated. The reddish residue was dissolved in 50 ml of tetrahydrofuran and treated at 0° under argon with 5 ml of lithium borohydride solution (2M in tetrahydrofuran). The reaction mixture was stirred at 0° for 30 minutes and then poured into 50 g of ice, 50 ml of saturated ammonium chloride solution and diethyl ether. The aqueous phase was extracted twice with ethyl acetate and the combined organic phases were dried over MgSO4 and evaporated. The residue was chromatographed on 200 g of silica gel with ethyl acetate/hexane (2:1), whereupon, after drying in a high vacuum, 3.90 g (88.1%) of 3,7-dimethoxy-6-[[(2-methoxyethoxy)-methoxy]methyl]-10-methyl-10H-dibenzo[b,e][1,4]oxazine-4-methanol were obtained as a colourless solid of m.p. 68°-70°.

Workup

  1. customwas brought slowly to 0°
  2. stirringstirred at 0° for 30 minutes
  3. extractionThe aqueous phase was extracted three times with chloroform
  4. dry with materialthe combined organic phases were dried over MgSO4
  5. customevaporated
  6. dissolutionThe reddish residue was dissolved in 50 ml of tetrahydrofuran
  7. additiontreated at 0° under argon with 5 ml of lithium borohydride solution (2M in tetrahydrofuran)
  8. stirringThe reaction mixture was stirred at 0° for 30 minutes
  9. additionpoured into 50 g of ice, 50 ml of saturated ammonium chloride solution and diethyl ether
  10. extractionThe aqueous phase was extracted twice with ethyl acetate
  11. dry with materialthe combined organic phases were dried over MgSO4
  12. customevaporated
  13. customThe residue was chromatographed on 200 g of silica gel with ethyl acetate/hexane (2:1), whereupon
  14. customafter drying in a high vacuum

Sources & evidence

ORD record
ord-4dbe97e9b87648419ecbbf8da7b88601
Source dataset
uspto-grants-1998_09
Patent number
US05811389

Reaction notes

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